The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index; none of the 25 sources its claims cite is checked for support yet.
Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
Open accessAbstract
The c-jun N-terminal kinase (JNK) signaling pathway is regulated by JNK-interacting protein-1 (JIP1), which is a scaffolding protein assembling the components of the JNK cascade. Overexpression of JIP1 deactivates the JNK pathway selectively by cytoplasmic retention of JNK and thereby inhibits gene expression mediated by JNK, which occurs in the nucleus. Here, we report the crystal structure of human JNK1 complexed with pepJIP1, the peptide fragment of JIP1, revealing its selectivity for JNK1 over other MAPKs and the allosteric inhibition mechanism. The van der Waals contacts by the three residues (Pro157, Leu160, and Leu162) of pepJIP1 and the hydrogen bonding between Glu329 of JNK1 and Arg156 of pepJIP1 are critical for the selective binding. Binding of the peptide also induces a hinge motion between the N- and C-terminal domains of JNK1 and distorts the ATP-binding cleft, reducing the affinity of the kinase for ATP. In addition, we also determined the ternary complex structure of pepJIP1-bound JNK1 complexed with SP600125, an ATP-competitive inhibitor of JNK, providing the basis for the JNK specificity of the compound.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
30 Own result · 26 Own interpretation · 20 Not checked yet · 3 No basis given · 1 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Binding of the peptide also induces a hinge motion between the Nand C-terminal domains of JNK1”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the small size of SP600125 (molecular weight ¼ 220), it effectively occupies the hydrophobic pocket of the ATP-binding site in JNK1”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As a result of the high homology of sequences with 92% identity, the overall architecture of JNK1 is substantially equal to that of JNK3 (PDB entry 1JNK; Xie et al , 1998).”
What the sources say
- Not checked yetcites Xie et al , 1998 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we have determined the crystal structure of JNK1 in complex with pepJIP1, the docking site peptide of JIP1 (residues 153-163), at a resolution of 2.35 A ˚ .”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“and distorts the ATPbinding cleft”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Leu160 and Leu162 of the f A-Xf B motif in pepJIP1 are extensively surrounded by many hydrophobic residues of JNK1 including Met121, Val118, Leu115, Ala113, Leu123, Val59, Leu131, and Cys163”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Arg156 ( f A 4) interacts with Glu329 with a bidentate salt bridge of length 2.70 A ˚ .”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also determined the structure of the ternary complex JNK1-pepJIP1-SP600125 at a resolution of 2.7 A ˚ .”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“reducing the affinity of the kinase for ATP.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is the first structure demonstrating the way by which MAPKs are selectively regulated by their scaffolding proteins.”
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 28
- Probably not a substantial claim. 6
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The K d values for pepJIP1 to bind to wild type, R127A, and E329A were found to be 0.42 7 0.13, 6.4 7 2.2, and 9.1 7 3.4 m M, respectively”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The peptide docks to the docking groove of JNK1, a surface of the Cterminal domain covering a 2, a 3, a 13, and b 8, which is away from the ATP pocket or substrate recognition site”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this structure, it is found that the docking site of the scaffolding protein also binds at the same docking grooves of JNK1 as the upstream kinase and the substrate transcription factor do in p38 MAPK (Chang et al , 2002), but with quite different interaction modes.”
What the sources say
- Not checked yetcites Chang et al , 2002 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Much more residues of the phosphorylation loop of the JNK1 complex are disordered than the JNK3 structure (missing residues 175-187 in JNK1-pepJIP1 and 212-216 in JNK3) although their ordered regions adopt a similar conformation”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most interesting result of the pepJIP1 binding to JNK1 is the rotation of the N-terminal domain relative to the Cterminal domain by approximately 15 1 , thereby distorting the ATP-binding site and inducing disorder of the phosphorylation loop”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most striking feature of the present structure is the distortion of the ATP-binding site induced by the interdomain rearrangement upon pepJIP1 binding, providing another mechanism of allosteric inhibition of the kinase activity by interfering with productive binding of ATP.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hinge motion is triggered in b 8, which interacts with Leu162 ( f B) by van der Waals contacts, and is propagated to the N-terminal domain via the single loop, which connects b 7 and b 8.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fortunately, the small molecule, SP600125, occupied the deepest adenine-binding site only, not expanding to the phosphate-binding site”
boostedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most notable difference is that the f A-Xf B motif of pepJIP1, especially Leu162 ( f B), is shifted by the structural difference between JNK1 and p38 in the region containing the hydrophobic residues critical for the f A-Xf B motif binding. In this region, JNK1 forms a oneturn helix ( a 2), but a two-turn helix in p38.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in the structure of the JNK1-pepJIP1 complex, the a 1 helix moved too far away for such interactions to occur as a result of the interdomain rearrangement upon pepJIP1 binding, and this loss of interactions released the phosphorylation loop of JNK1pepJIP1 from the N-terminal domain, resulting in the increased disorder of the loop.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The root-mean-square (r.m.s.) deviations for C a atoms of the Nand C-terminal domain between the structures of JNK1-pepJIP1 and JNK3 are 1.27 and 0.79 A ˚ , respectively. These values show that there is no significant structural difference between the corresponding domains.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, the overexpression of either the domain within JIP1 that binds to JNK, or the full-length protein, potently inhibits JNK signaling in the cell (Dickens et al , 1997).”
What the sources say
- Not checked yetcites Dickens et al , 1997 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“JNK-interacting protein-1 (JIP1) was identified as a scaffolding protein of the JNK module in yeast two-hybrid analysis, enhancing the correspondent signaling through the pathway (Whitmarsh et al , 1998).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the structure, the INK4 inhibitors bind next to the ATP-binding site, opposite where the activating cyclin binds, and thereby not only prevent cyclin binding indirectly but also reduce the affinity of the kinase for ATP by causing extensive allosteric changes in CDK6.”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This implies that JNK and p38 may act as chemomechanical energy transducers, using peptide binding energy to generate allosteric conformational changes (Goldsmith, 1996).”
What the sources say
- Not checked yetcites Goldsmith, 1996 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, similar but nonidentical docking grooves in each MAPKs appear to be the important determinant of pathway specificity in addition to the variations in sequences of docking sites.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“And the size of the pocket may also be connected with the intrinsic flexibility of the loops around the catalytic cleft in protein kinases, and the diverse modes of the flexibility dependent on each protein kinases could be important determinants of the selectivity of SP600125.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SP600125 is a reversible ATPcompetitive inhibitor with more than 20-fold selectivity over other kinases including Erk, p38 MAPKs, MKKs, and PKCs.”
What the sources say
- Not checked yetcites Bennett et al , 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, the structure of JNK3 in complex with SP600125 was reported (PDB entry 1PMV; Scapin et al , 2003).”
What the sources say
- Not checked yetcites Scapin et al , 2003 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In cells, SP600125 dose-dependently inhibited the phosphorylation of c-jun, the expression of inflammatory genes COX-2, IL2, IHNg , and TNFa , and prevented the activation and differentiation of human CD4 cell.”
What the sources say
- Not checked yetcites Bennett et al , 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The latest result demonstrates that the JNK specificity of SP600125 is not so excellent and this compound inhibits some protein kinases with similar or greater potency than JNK (Bain et al , 2003).”
What the sources say
- Not checked yetcites Bain et al , 2003 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This distortion would not eliminate the ATP binding, but it would significantly reduce ATP affinity and may well disorient any bound ATP with respect to the kinase catalysis, and thus inhibit the JNK activity to phosphorylate the substrates.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the release of the phosphorylation loop, when JNK binds to the JIP1 scaffolding protein, may give a chance for the loop to refold and take an appropriate conformation to be recognized and phosphorylated by MKKs, which are also scaffolded in JIP1, and be ready to recognize the substrates.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the docking site can be characterized by not only the sequential similarity of the f A-Xf B motifs but also the conformational conservation of the motifs in their structures.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In in vivo studies in mice, SP600125 inhibited lipopolysaccharide-induced expression of TNFa and prevented anti-CD3-mediated thymocyte apoptosis (Bennett et al , 2001).”
What the sources say
- Not checked yetcites Bennett et al , 2001 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In other words, the inhibition of the full-length JIP1 in vivo is more complicated than that of pepJIP1, and the structural feature of the inhibition by full-length JIP1 might have significant differences from that of pepJIP1.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The docking groove of JNK1 is expected to accommodate the docking sites of MKK7 or c-jun as that of p38 does, but there may exist other important determinants than the interaction by Arg156 ( f A 4) of JIP1 for specific recognition of the docking sites of MKK7 or c-jun because this residue is not conserved in the sequential comparison (Figure 1D).”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Phosphorylation of JNK by MKKs and activation of c-jun by JNK also might undergo such an interdomain rearrangement as the JNK1-pepJIP1 complex due to the intrinsic flexibility of the loops around the catalytic cleft.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These previous studies imply that therapeutic inhibition of JNK has significant potential in inflammatory disease, acute organ failure due to apoptotic cell death, and cancer.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that the N- and C-terminal domains are linked by only two loops, the loop connecting b 7 and b 8 and the disordered 331-351 loop, implies that the intrinsic flexibility may exist in the kinase, and the inherent structural flexibility may play a central role in its regulation upon JIP1 binding to JNK1.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
SP600125 has similar potency against the JNK1, JNK2, and JNK3 isoforms.
“SP600125 inhibited JNK1, 2, and 3 isoforms with similar potency”
The paper relies on this without support.
The hydrophobic residues in the adenine-binding pocket are conserved across JNK isoforms.
“all of the hydrophobic residues are conserved in JNK isoforms.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, only three hydrophobic pockets (U A , U B , and U L ) are present in JNKs [Fig.2(A)].46,51,52”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [51]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Similarly, while both electrostatic pockets (W L, W U ) are present and occupied by different KIM peptides in ERK, p38, and FUS3, only the W L pocket is engaged by KIM peptides that bind specifically to JNKs [Fig.2(A)].”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [51]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The two docking peptides adopted different main chain conformations between the contact points corresponding to the D-motif consensus sequence.”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [13]
Experimental — accuracy not yet measuredIn the citing paper
“The structure of JNK1 bound to a peptide from JIP1 protein showed that the peptide induced a rotation of the two lobes that distorted the active site, which was proposed as a mechanism for JIP1-mediated inhibition of JNK signaling (Heo et al., 2004).”
From Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases (2012) · cites this paper as Heo et al., 2004
In the citing paper
“In the initial publication of JIP1-bound JNK (Heo et al., 2004), the interlobe rotation was apparent, but not the more substantial lobe opening, nor the mechanism of allosteric signal transduction, due to the inherent limitations of examining a single structure.”
From Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases (2012) · cites this paper as Heo et al., 2004
In the citing paper
“At the structural level, MAPK docking is a well characterized protein-peptide interaction system (9, 12-16).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Disorder of the phosphorylation loop
“missing residues 175-187 in JNK1-pepJIP1 and 212-216 in JNK3”
§ Structure determination and refinement
“The final model contained one JNK1 molecule of residues 9-172, 190-281, 287-336, and 349-363, one pepJIP1 molecule of residues 154-163, and 97 water molecules.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Interdomain rearrangement mediated by pepJIP1 binding
“pepMEF2A (saturated red) or pepMKK3b (saturated blue) bound in p38 MAPK (whitened blue)”
§ Interdomain rearrangement mediated by pepJIP1 binding
“The residues of pepJIP1, pepMEF2A, and pepMKK7 are labeled black, red, and blue, respectively.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Interdomain rearrangement mediated by pepJIP1 binding
“And the structure of E327 of JNK1 is compared with those of the corresponding glutamates of JNK3 (green), p38 (blue), and Erk2 (pink).”
§ pepJIP1 as a JNK-specific inhibitor
“And the fact that the structure of Glu329 of JNK1 complexed with pepJIP1 is actually identical to that of Glu367 of free JNK3”
Citations
Cites
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,723
Signal transduction by the JNK group of MAP kinases
Davis, R. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00116-1 · Cited by 4,237
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558
Protein modules and signalling networks
Pawson, T. (1995) · Nature · doi:10.1038/373573a0 · Cited by 2,420
Signaling Through Scaffold, Anchoring, and Adaptor Proteins
Pawson, T., & Scott, J. D. (1997) · Science · doi:10.1126/science.278.5346.2075 · Cited by 2,256
The specificities of protein kinase inhibitors: an update
BAIN, J., McLAUCHLAN, H., ELLIOTT, M., & COHEN, P. (2003) · Biochemical Journal · doi:10.1042/bj20021535 · Cited by 1,369 · cited 4×
“The latest result demonstrates that the JNK specificity of SP600125 is not so excellent and this compound inhibits some protein kinases with similar or greater potency than JNK ( Bain et al, 2003 ).”
BackgroundResultInfluentialSelective interaction of JNK protein kinase isoforms with transcription factors.
Gupta, S., Barrett, T., Whitmarsh, A. J., Cavanagh, J., Sluss, H. K., Dérijard, B., & Davis, R. J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00636.x · Cited by 1,341
Organization and regulation of mitogen-activated protein kinase signaling pathways
Garrington, T. P., & Johnson, G. L. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80028-3 · Cited by 1,268
Cited by
Sorted by citations
ERK1/2 MAP kinases: Structure, function, and regulation
Roskoski, R. J. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.04.005 · Cited by 1,719
“Based upon X-ray crystallographic studies, the A-X- B sequences within D-sites bind to mouse p38 [110] and human JNK1 [111] in a hydrophobic groove flanked by helices D and E and the 7- 8 reverse turn.”
BackgroundThe JNK signal transduction pathway
Weston, C. R. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(01)00258-1 · Cited by 1,551
Mechanisms of specificity in protein phosphorylation
Ubersax, J. A., & Ferrell Jr, J. E. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2203 · Cited by 1,451
“Interestingly, other docking-site interactions appear to negatively regulate the docked kinas”
BackgroundDifferential regulation and properties of MAPKs
Raman, M., Chen, W., & Cobb, M. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210392 · Cited by 1,430
“Structural insights and regulation via docking domains Crystal structures of JNK3a1 bound to adenylylimidodiphosphate (AMP-PNP) and JNK1 complexed with a peptide from the scaffold JNK interacting protein 1 (JIP1) showed overall architecture similar to ERK2 and p38 (Heo et al., 2004).”
BackgroundNolen, B. J., Taylor, S. S., & Ghosh, G. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.08.024 · Cited by 1,171
The JNK signal transduction pathway
Weston, C. R., & Davis, R. J. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.001 · Cited by 1,021
“Recent studies have provided insight into the structure of JIP complexes, with reports describing the atomic structure of the JIP/JNK interaction [33] and the SH3/SH3 dimerization interface between JIP1 molecules [34].”
BackgroundUses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases
Bogoyevitch, M. A., & Kobe, B. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00025-06 · Cited by 584
Cell Signaling and Stress ResponsesPreprint
Hotamışlıgil, G. S., & Davis, R. J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006072 · Cited by 512
“JNK1 and JNK2 are ubiquitously expressed, but JNK3 is expressed primarily in the brain (Davis 2000).”
BackgroundInfluentialBhattacharyya, R. P., Reményi, A., Yeh, B. J., & Lim, W. A. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142710 · Cited by 458
MAP kinases and the control of nuclear events
Turjanski, A. G., Vaque, J. P., & Gutkind, J. S. (2007) · Oncogene · doi:10.1038/sj.onc.1210415 · Cited by 439
“…provided insights into the dynamic conformational changes occurring on MAPKs upon binding to upstream activators, scaffolds and downstream targets (Heo et al., 2004; Hoofnagle et al., 2004; Lee et al., 2005; Zhou et al., 2006), which can also contribute to the signaling specificity of each MAPK…”
BackgroundInfluentialFrom JNK to Pay Dirt: Jun Kinases, their Biochemistry, Physiology and Clinical Importance
Karin, M., & Gallagher, E. D. (2005) · IUBMB Life · doi:10.1080/15216540500097111 · Cited by 414
JNK signalling in cancer: in need of new, smarter therapeutic targets
Bubici, C., & Papa, S. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12432 · Cited by 355
“MAPKs are activated via a BJP British Journal ofPharmacology DOI:10.1111/bph.12432 www.brjpharmacol.org 24 British Journal of Pharmacology (2014) 171 24–37 © 2013 The British Pharmacological Society kinase signalling cascade in which a MAP3K activates a MAP2K, that in turn activates a MAPK.”
BackgroundInfluentialc-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges
Bogoyevitch, M. A., Ngoei, K. R. W., Zhao, T. T., Yeap, Y. Y. C., & Ng, D. C. H. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.002 · Cited by 335
“The structures of JNK3 and JNK1 have been reported [17,18], and often these have been in complex with small molecule ATP-competitive inhibitors (e.”
BackgroundMolecular basis of MAP kinase regulation
Peti, W., & Page, R. (2013) · Protein Science · doi:10.1002/pro.2374 · Cited by 302
“2(A)].(46,51,52) Similarly, while both electrostatic pockets (WL, WU) are present and occupied by different KIM peptides in ERK, p38, and FUS3, only the WL pocket is engaged by KIM peptides that bind specifically to JNKs [Fig.”
BackgroundTargeting innate immunity protein kinase signalling in inflammation
Gaestel, M., Kotlyarov, A., & Kracht, M. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2829 · Cited by 323
“Interestingly, the JIP1 peptide distorts the ATP binding site of JNK, which suggests that binding of scaffolds, activators or substrates to JNK is an additional determinant of the affinity of ATP-competitive inhibitors such as SP60012”
BackgroundRequirement of JNK2 for Scavenger Receptor A-Mediated Foam Cell Formation in Atherogenesis
Ricci, R., Sumara, G., Sumara, I., Rozenberg, I., Kurrer, M. O., Akhmedov, A., Hersberger, M., Eriksson, U., Eberli, F. R., Becher, B., et al. (2004) · Science · doi:10.1126/science.1101909 · Cited by 278
Babon, J. J., Kershaw, N. J., Murphy, J. M., Varghese, L. N., Laktyushin, A., Young, S. N., Lucet, I. S., Norton, R. S., & Nicola, N. A. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.015 · Cited by 279
“Other inhibitors act by competitive mechanisms, either by blocking the active site directly, for example p27KIP1 (Russo et al., 1996) and RKIP (Yeung et al., 1999), or by disrupting it allosterically, for example JIP (Barr et al., 2004; Heo et al., 2004).”
Mechanisms of MAPK signalling specificity
Bardwell, L. (2006) · Biochemical Society Transactions · doi:10.1042/bst0340837 · Cited by 217
Role of the AP-1 transcription factor c-Jun in developing, adult and injured brain
Raivich, G., & Behrens, A. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.03.006 · Cited by 225
Fang, Z., Grütter, C., & Rauh, D. (2013) · ACS Chemical Biology · doi:10.1021/cb300663j · Cited by 197
Arkin, M. R., & Whitty, A. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.05.125 · Cited by 190
Docking interactions in protein kinase and phosphatase networks
Reményi, A., Good, M. C., & Lim, W. A. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.10.008 · Cited by 188
Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove
Garai, Á., Zeke, A., Gógl, G., Törő, I., Fördős, F., Blankenburg, H., Bárkai, T., Varga, J., Alexa, A., Emig, D., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2003004 · Cited by 177
Approaches to discover non-ATP site kinase inhibitors
Gavrin, L. K., & Saiah, E. (2012) · MedChemComm · doi:10.1039/c2md20180a · Cited by 186
Identification of a new JNK inhibitor targeting the JNK-JIP interaction site
Stebbins, J. L., De, S. K., Machleidt, T., Becattini, B., Vazquez, J., Kuntzen, C., Chen, L.-H., Cellitti, J. F., Riel-Mehan, M., Emdadi, A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805677105 · Cited by 186
“In addition, an extensive network of hydrogen bonding interactions is predicted between the triazole, nitro group, and thiazole of BI-78D3 with JNK1 R127, an interaction that has been demonstrated as critical for pepJIP1 binding to JNK1 (17).”
BackgroundResultInfluentialReceptor for RACK1 Mediates Activation of JNK by Protein Kinase C
Lopez‐Bergami, P., Habelhah, H., Bhoumik, A., Zhang, W., Wang, L., & Ronai, Z. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.06.025 · Cited by 186
“[PubMed: 11716513] Heo YS, Kim SK, Seo CI, Kim YK, Sung BJ, Lee HS, Lee JI, Park SY, Kim JH, Hwang KY, et al. Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125.”
BackgroundMehan, S., Meena, H., Sharma, D., & Sankhla, R. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9454-6 · Cited by 185
“Apart from amino acid sequences and transcript modifications, the crystal structures of JNK1 (Heo et al. 2004) and JNK3 (Xie et al. 1998) have been published.”
BackgroundDocking Interactions Induce Exposure of Activation Loop in the MAP Kinase ERK2
Zhou, T., Sun, L., Humphreys, J., & Goldsmith, E. J. (2006) · Structure · doi:10.1016/j.str.2006.04.006 · Cited by 164
Substrate and Docking Interactions in Serine/Threonine Protein Kinases
Goldsmith, E. J., Akella, R., Min, X., Zhou, T., & Humphreys, J. M. (2007) · Chemical Reviews · doi:10.1021/cr068221w · Cited by 143
Bogoyevitch, M. A., & Fairlie, D. P. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.06.008 · Cited by 164
Reményi, A., Good, M. C., Bhattacharyya, R. P., & Lim, W. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.030 · Cited by 154
“Interestingly, the interaction of the docking peptide from Jip1 with the mammalian MAPK JNK1 also appears to occur via a mechanism similar to mode 2 (Figure S6).”
BackgroundShiwen, X., Rodríguez‐Pascual, F., Lamas, S., Holmes, A. M., Howat, S., Pearson, J. D., Dashwood, M. R., du Bois, R. M., Denton, C. P., Black, C. M., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00625-06 · Cited by 159
“Similarly, overexpression of JIP-1, which selectively deactivates the JNK pathway by cytoplasmic retention of JNK ( 24 ), inhibited the TGF- induction of ET-1 in normal fibroblasts of gene expression mediated by JNK, which occurs in the nucleus.”
BackgroundSheridan, D. L., Kong, Y., Parker, S. A., Dalby, K. N., & Turk, B. E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801074200 · Cited by 147
Fabre, T., Kared, H., Friedman, S. L., & Shoukry, N. H. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400861 · Cited by 150
Manipulation of host signalling pathways by anthrax toxins
Turk, B. E. (2007) · Biochemical Journal · doi:10.1042/bj20061891 · Cited by 149
Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3
Liu, S., Sun, J.-P., Zhou, B., & Zhang, Z.-Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510506103 · Cited by 140
Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase
Zhu, Y., Li, H., Long, C., Hu, L., Xu, H., Liu, L., Chen, S., Wang, D., & Shao, F. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.011 · Cited by 133
“D motifs from several MAPK-binding proteins have been cocrystallized with MAPKs, suggesting that it is sufficient for MAPK binding (Chang et al., 2002; Farooq et al., 2001; Heo et al., 2004; Zhou et al., 2006).”
BackgroundErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
Yamauchi, J., Miyamoto, Y., Chan, J. R., & Tanoue, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200709033 · Cited by 131
Selectivity of Docking Sites in MAPK Kinases
Bardwell, A. J., Frankson, E., & Bardwell, L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900080200 · Cited by 127
Inhibitors of c-Jun N-terminal kinases—JuNK no more?
Bogoyevitch, M. A., & Arthur, P. G. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.09.013 · Cited by 129
“These JIP-derived peptides inhibitors have been shown kinetically to act in a protein substrate-competitive manner [79], and by cocrystallisation and mutagenesis studies to bind directly to the putative protein substrate docking domain of JNK [80,81].”
BackgroundTargeting JNK3 for the treatment of neurodegenerative disorders
Resnick, L., & Fennell, M. (2004) · Drug Discovery Today · doi:10.1016/s1359-6446(04)03251-9 · Cited by 128
Microtubule and microtubule associated protein anomalies in psychiatric disease
Marchisella, F., Coffey, E. T., & Hollós, P. (2016) · Cytoskeleton · doi:10.1002/cm.21300 · Cited by 132
Therapeutic targets for rheumatoid arthritis: Progress and promises
Alghasham, A., & Rasheed, Z. (2014) · Autoimmunity · doi:10.3109/08916934.2013.873413 · Cited by 118
“VX-745 Inhibitor of p38a, p38b and p38g [170] VX-702 p38a inhibitor [171,172] SB-203580 Inhibitor of p38a and p38b [173] SB-731445 Inhibitor of p38a and p38b [173] BIRB-796 Inhibitor of all p38MAPK: p38a/b/g/ [173] SCIO-323 p38a inhibitor [173] AMG-548 p38a inhibitor [172] Pamapimond p38a inhibitor [172] (b) JNK-MAPKs…”
Ablation of the spindle assembly checkpoint by a compound targeting Mps1
Schmidt, M., Budirahardja, Y., Klompmaker, R., & Medema, R. H. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400483 · Cited by 120
Structural and Functional Characterization of the Human Protein Kinase ASK1
Bunkòczi, G., Salah, E., Filippakopoulos, P., Fedorov, O., Müller, S., Sobott, F., Parker, S. A., Zhang, H., Wang, M., Turk, B. E., et al. (2007) · Structure · doi:10.1016/j.str.2007.08.011 · Cited by 110
“In MAPKs, D motif docking peptides bind at analogous sites to p38a and JNK1 and induce conformational changes unique to each kinase (Chang et al., 2002; Heo et al., 2004).”
BackgroundMolecular basis of MAPK-activated protein kinase 2:p38 assembly
White, A., Pargellis, C. A., Studts, J. M., Werneburg, B. G., & Farmer, B. T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701679104 · Cited by 111
Unique MAP Kinase binding sites
Akella, R., Moon, T. M., & Goldsmith, E. J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.09.016 · Cited by 108
“Crystallographic studies of p38α [41] and JNK1 [44] revealed the hydrophobic groove to be near helices D and E.”
BackgroundAkakpo, J. Y., Ramachandran, A., Duan, L., Schaich, M. A., Jaeschke, M. W., Freudenthal, B. D., Ding, W.-X., Rumack, B. H., & Jaeschke, H. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz077 · Cited by 105
“This would render its inhibition like that of SP600125, a hydrophobic ATP-competitive JNK inhibitor (Heo et al., 2004).”
BackgroundYan, H., He, L., Lv, D., Yang, J., & Yuan, Z. (2024) · Biomolecules · doi:10.3390/biom14020243 · Cited by 112
“The crystal structures of the three JNK isoforms were determined, showing over 90% sequence homology [20–22].”
BackgroundMinor introns are embedded molecular switches regulated by highly unstable U6atac snRNA
Younis, I., Dittmar, K. A., Wang, W., Foley, S. W., Berg, M. G., Hu, K. Y., Wei, Z., Wan, L., & Dreyfuss, G. (2013) · eLife · doi:10.7554/elife.00780 · Cited by 98
“Because anisomycin activates both p38MAPK and JNK, we pre-treated cells with either SB203580, an inhibitor of p38MAPK activation (Davies et al., 2000), or SP600125, an inhibitor of JNK (Heo et al., 2004).”
MethodInhibitors of c-Jun N-Terminal Kinases: An Update
Koch, P., Gehringer, M., & Laufer, S. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501212r · Cited by 103
Fructose-mediated stress signaling in the liver: implications for hepatic insulin resistance
Wei, Y., Wang, D., Topczewski, F., & Pagliassotti, M. J. (2006) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2006.03.013 · Cited by 100
“[94] Heo Y-S, Kim S-K, Seo CI, Kim YK, Sung B-J, Lee HS, et al.”
BackgroundDávila, D., & Torres‐Alemán, I. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-08-0811 · Cited by 98
De, S. K., Stebbins, J. L., Chen, L., Riel-Mehan, M. M., Machleidt, T., Dahl, R. S., Yuan, H., Emdadi, A., Barile, E., Chen, V., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801503n · Cited by 95
Specific activities of individual c-Jun N-terminal kinases in the brain
Haeusgen, W., Boehm, R., Zhao, Y., Herdegen, T., & Waetzig, V. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.04.014 · Cited by 92
Structure and dynamics of the MKK7–JNK signaling complex
Kragelj, J., Palencia, A., Nanao, M., Maurin, D., Bouvignies, G., Blackledge, M. J., & Jensen, M. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419528112 · Cited by 86
Dixit, A., & Verkhivker, G. M. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002179 · Cited by 83
Delaforge, E., Kragelj, J., Tengo, L., Palencia, A., Milles, S., Bouvignies, G., Salvi, N., Blackledge, M. J., & Jensen, M. R. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b12407 · Cited by 85
Comess, K. M., Sun, C. C., Abad‐Zapatero, C., Goedken, E. R., Gum, R. J., Borhani, D. W., Argiriadi, M. A., Groebe, D. R., Jia, Y., Clampit, J. E., et al. (2010) · ACS Chemical Biology · doi:10.1021/cb1002619 · Cited by 80
Structural basis of p38α regulation by hematopoietic tyrosine phosphatase
Francis, D. M., Różycki, B., Koveal, D., Hummer, G., Page, R., & Peti, W. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.707 · Cited by 79
Networks for the allosteric control of protein kinases
Shi, Z., Resing, K. A., & Ahn, N. G. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.10.011 · Cited by 78
Kinase Atlas: Druggability Analysis of Potential Allosteric Sites in Kinases
Yueh, C., Rettenmaier, J., Xia, B., Hall, D. R., Alekseenko, A. E., Porter, K. A., Barkovich, K. J., Keserű, G. M., Whitty, A., Wells, J. A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00089 · Cited by 75
Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies
Oliinyk, O. S., Baloban, M., Clark, C. L., Carey, E. M., Pletnev, S. V., Nimmerjahn, A., & Verkhusha, V. V. (2022) · Nature Methods · doi:10.1038/s41592-022-01467-6 · Cited by 73
“The binding of this peptide induces rearrangement between the N-and C-terminal domains of JNK and distorts the ATP-binding pocket, inhibiting the catalytic activity 56 .”
Small Molecule JNK (c-Jun N-Terminal Kinase) Inhibitors
Siddiqui, M. A., & Reddy, P. A. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm9003279 · Cited by 76
Jnawali, H. N., Lee, E., Jeong, K., et al. (2014) · Journal of Natural Products · doi:10.1021/np400803n · Cited by 75
Self-citationPeptide inhibitors of protein kinases—discovery, characterisation and use
Bogoyevitch, M. A., Barr, R. K., & Ketterman, A. J. (2005) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2005.07.025 · Cited by 77
Chambers, J. W., Howard, S., & LoGrasso, P. V. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.421354 · Cited by 72
Kamenecka, T., Habel, J. E., Duckett, D. R., Chen, W., Ling, Y. Y., Frąckowiak, B., Jiang, R., Shin, Y., Song, X., & LoGrasso, P. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809430200 · Cited by 72
Diskin, R., Lebendiker, M., Engelberg, D., & Livnah, O. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.08.043 · Cited by 72
Ho, D. T., Bardwell, A. J., Grewal, S., Iverson, C., & Bardwell, L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601010200 · Cited by 70
Elgazar, A. A., Selim, N. M., Abdel‐Hamid, N. M., et al. (2018) · Phytotherapy Research · doi:10.1002/ptr.6056 · Cited by 70
“On the other hand, only the diarylheptanoids could to some extent occupy the hydrophobic pocket (Ile32, Val40, Ala53, Ile86, Met108, Leu110, Val158, and Leu168) with effective Van der Waals contacts, which is responsible for the JNK inhibition specificity (Heo et al., 2004).”
BackgroundZeke, A., Bastys, T., Alexa, A., Garai, Á., Mészáros, B., Kirsch, K., Dosztányi, Z., Kalinina, O. V., & Reményi, A. (2015) · Molecular Systems Biology · doi:10.15252/msb.20156269 · Cited by 70
“For some motif classes, a reliable crystallographic model was available because the JNK1-pepJIP1 and JNK-pepNFAT4 complex crystal structures contained full consensus motifs (Heo et al, 2004; Garai et al, 2012).”
InfluentialDesign and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3
Swahn, B., Huerta, F. F., Kallin, E., Malmström, J., Weigelt, T., Viklund, J., Womack, P., Xue, Y., & Öhberg, L. M. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.06.083 · Cited by 70
Tumor Cell Phenotype Is Sustained by Selective MAPK Oxidation in Mitochondria
Galli, S., Arciuch, V. G. A., Poderoso, C., Converso, D. P., Zhou, Q., Joffé, E. B. D. K., Cadenas, E., Boczkowski, J., Carreras, M. C., & Poderoso, J. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002379 · Cited by 71
“MAPKs are specifically regulated by a MAPK kinase (MAPKK) [22], i.e., ERK1/2 is activated by MEK1/2, p38 by MKK3, and JNK1/2 by MKK4, among others.”
BackgroundInfluentialSelim, N. M., Elgazar, A. A., Abdel‐Hamid, N. M., El‐Magd, M. A., Yasri, A., El-Hefnawy, H. M., & Sobeh, M. (2019) · Antioxidants · doi:10.3390/antiox8090371 · Cited by 65
“The binding in the ATP active site of ERK1/2 requires the interaction with the gate keeper residues (Gln-105), hinge region (Met-108), while selectivity could be achieved by interaction with the so-called glycine rich loop (Tyr-36, Ile-56 and Gly-34) [38].”
BackgroundChu, M. L.-H., Chavas, L. M. G., Douglas, K. T., Eyers, P. A., & Tabernero, L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803026200 · Cited by 70
Li, C., MacDonald, J. I., Hryciw, T., & Meakin, S. O. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06507.x · Cited by 62
Stogios, P. J., Spanogiannopoulos, P., Evdokimova, E., Egorova, O., Shakya, T., Todorovic, N., Capretta, A. A., Wright, G. D., & Savchenko, A. V. (2013) · Biochemical Journal · doi:10.1042/bj20130317 · Cited by 60
Non-ATP competitive protein kinase inhibitors as anti-tumor therapeutics
Kirkland, L. O., & McInnes, C. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.12.022 · Cited by 60
Murakami, Y., Tatebayashi, K., & Saito, H. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01817-07 · Cited by 59
“... structures of the extracellular signal-regulated kinase (ERK), Jun N-terminal protein kinase, and p38 subfamilies of mammalian MAPKs show that the L16 segment starts within the C-terminal lobe, climbs up along the linker region between the N- and C-terminal lobes on the other side of the ATP-binding cleft, and ter…”
BackgroundDai, Y., Rahmani, M., Pei, X., Khanna, P., Han, S. I., Mitchell, C., Dent, P., & Grant, S. (2004) · Blood · doi:10.1182/blood-2004-07-2767 · Cited by 61
Barr, R. K., Boehm, I., Attwood, P. V., Watt, P. M., & Bogoyevitch, M. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402181200 · Cited by 61
Pellegrini, E., Palencia, A., Braun, L., Kapp, U., Bougdour, A., Belrhali, H., Bowler, M. W., & Hakimi, M. (2016) · Structure · doi:10.1016/j.str.2016.10.011 · Cited by 54
“The CD domain accommodates thefU and basic residues, while the hydrophobic docking groove binds fA, fB, and fL (Akella et al., 2010; Heo et al., 2004; Lee et al., 2006).”
BackgroundShaw, D. E., Wang, S. M., Villaseñor, A. G., Tsing, S., Walter, D., Browner, M. F., Barnett, J. W., & Kuglstatter, A. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.08.086 · Cited by 59
Scaffold proteins as dynamic integrators of biological processes
DiRusso, C. J., Dashtiahangar, M., & Gilmore, T. D. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102628 · Cited by 61
“(2022) 298(12) 102628 been documented by structural approaches, including X-ray crystallography (XRC), NMR, small angle X-ray scattering (SAXS), and cryo-EM, or by computational modeling based on existing crystal structures.”
BackgroundLiu, X., Zhang, C., Lu, C., Lin, S., Wu, J., & Wang, Z. (2016) · Nature Communications · doi:10.1038/ncomms10879 · Cited by 58
Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin
Jnawali, H. N., Jeon, D., Jeong, M., et al. (2016) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5b01033 · Cited by 59
Self-citationc-Jun N-terminal kinases in memory and synaptic plasticity
Sherrin, T., Blank, T., & Todorovic, C. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.032 · Cited by 56
Ethanol rapidly causes activation of JNK associated with ER stress under inhibition of ADH
Nishitani, Y., & Matsumoto, H. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.11.030 · Cited by 58
“On the other hand, it was also reported that the overexpression of the JIP1-peptide which binds to JNK inhibits JNK signaling [39].”
BackgroundJNK signaling pathway in metabolic disorders: An emerging therapeutic target
Garg, R., Kumariya, S., Katekar, R. A., Verma, S., Goand, U. K., & Gayen, J. R. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174079 · Cited by 57
Cheon, D., Kim, J., Jeon, D., Shin, H., & Kim, Y. (2019) · Molecules · doi:10.3390/molecules24071319 · Cited by 60
“JNK1 was purified as previously reported [47].”
Self-citationTruman, A. W., Kim, K.-Y., & Levin, D. E. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00794-09 · Cited by 57
Selective killing of p53‐deficient cancer cells by SP600125
Jèmaà, M., Vitale, I., Kepp, O., Berardinelli, F., Galluzzi, L., Senovilla, L., Mariño, G., Malik, S. A., Rello‐Varona, S., Lissa, D., et al. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200228 · Cited by 60
“…(880nM) and VEGFR3 (300nM) (Colombo et al, 2010), but best known for inhibiting c-Jun N-terminal kinases (JNK) 1–3 (100–200nM) (Bennett et al, 2001; Heo et al, 2004) and MPS1 (IC 50 1.95 m M) (Chu et al, 2008; Schmidt et al, 2005), was the most efficient agent in increasing the ratio between WT and…”
InfluentialMapping ERK2-MKP3 Binding Interfaces by Hydrogen/Deuterium Exchange Mass Spectrometry
Zhou, B., Zhang, J., Liu, S., Reddy, S., Wang, F., & Zhang, Z. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608916200 · Cited by 56
Zhang, Y.-Y., Wu, J.-W., & Wang, Z.-X. (2011) · Science Signaling · doi:10.1126/scisignal.2002241 · Cited by 52
Identification of small-molecule inhibitors of the JIP–JNK interaction
Chen, T. X., Kablaoui, N. M., Little, J., Timofeevski, S. L., Tschantz, W. R., Chen, P., Feng, J., Charlton, M. E., Stanton, R. V., & Bauer, P. H. (2009) · Biochemical Journal · doi:10.1042/bj20081899 · Cited by 55
c-JunN-terminal kinase inhibitors: a patent review (2010 – 2014)
Gehringer, M., Muth, F., Koch, P., & Laufer, S. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2015.1039984 · Cited by 56
“The peptidic portion of the molecules consists of truncated derivatives of D-domain-containing peptide pepJIP1 (M1, Figure 16), a known selective ligand of the JNK--JIP interaction site [58].”
BackgroundStructural and Functional Analysis of the Natural JNK1 Inhibitor Quercetagetin
Baek, S., Kang, N. J., Popowicz, G. M., Arciniega, M., Jung, S. K., Byun, S., Song, N. R., Heo, Y.-S., Kim, B. Y., Lee, H. J., et al. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.10.019 · Cited by 55
Self-citationProtein Kinase Inhibitors: Structural Insights Into Selectivity
Thaimattam, R., Banerjee, R., Miglani, R., & Javed Iqbal, M. (2007) · Current Pharmaceutical Design · doi:10.2174/138161207781757042 · Cited by 52
Wei, Y., Wang, D., & Pagliassotti, M. J. (2005) · Journal of Nutrition · doi:10.1093/jn/135.7.1642 · Cited by 54
Metadata
- Authors
- Heo, Y., Kim, S., Seo, C. I., Kim, Y. K., Sung, B., Lee, H. S., Lee, J. I., Park, S., Kim, J. H., Hwang, K. Y., Hyun, Y., Jeon, Y. H., Ro, S., Cho, J. M., Lee, T. G., & Yang, C.
- Affiliations
- Seoul National University (KR)
- CrystalGenomics (South Korea) (KR)
- Yokohama City University (JP)
- Corresponding author
- Lee, Tae Gyu
- Yang, Chul‐Hak
- ORCID
- Venue
- The EMBO Journal
- Published
- 2004-05-13
- Volume
- 23
- Issue
- 11
- Pages
- 2185-2195
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC419904
- OpenAlex
- W2132108032
- Semantic Scholar
- ea6807d2e0dc42824be4ee4eab16e61e43294855
- Cited by
- 275
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 14 · 2013: 17 · 2012: 21
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Research Institute of Bioscience and Biotechnology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- JNK1, JIP1, SP600125, c-Jun N-terminal kinase, MAPK signaling, allosteric inhibition, kinase specificity, peptide binding, hinge motion, ternary complex structure, scaffold proteins, crystal structure
- MeSH terms
- Adenosine Triphosphate, Allosteric Regulation, Anthracenes, Arginine, Binding Sites, Calorimetry, HeLa Cells, Humans, Hydrogen Bonding, Leucine, Models, Molecular, Proline, Protein Binding, Protein Conformation, Transfection, Blotting, Western, Signal Transduction, Protein Structure, Tertiary, Crystallography, X-Ray, Glutamic Acid, Mitogen-Activated Protein Kinase 8, Adaptor Proteins, Signal Transducing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-29, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-29 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
