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Cited by 275Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125

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Heo, Yong‐Seok, Kim, Su‐Kyoung, Seo, Chang Il, Kim, Young Kwan, Sung, Byung‐Je, Lee, Hye Shin, Lee, Jae Il, Park, Sam‐Yong +8 more·2004·The EMBO Journal
DOI 10.1038/sj.emboj.7600212PMC PMC419904
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Abstract

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.

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Crossref · 10.1038/sj.emboj.7600212

Cites

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Claims the paper makes

0 of 25 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125

    Binding of pepJIP1 induces a hinge motion between the N- and C-terminal domains of JNK1.

    “Binding of the peptide also induces a hinge motion between the Nand C-terminal domains of JNK1”
    Quote in the paperSubstantial claim
  • Findingown data
    § Introduction

    SP600125 effectively occupies the hydrophobic pocket of the ATP-binding site in JNK1 despite its small size.

    “Despite the small size of SP600125 (molecular weight ¼ 220), it effectively occupies the hydrophobic pocket of the ATP-binding site in JNK1”
    Quote in the paperSubstantial claim
  • Findingcitation
    § Overall structure of JNK1 complexed with pepJIP1

    The overall architecture of JNK1 is substantially equal to that of JNK3 due to 92% sequence identity.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Xie et al , 1998 source

      Not checked in the free run.

  • Findingown data
    § Introduction

    The crystal structure of human JNK1 in complex with pepJIP1 was determined at 2.35 Å resolution.

    “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 ˚ .”
    Quote in the paperSubstantial claim
  • Findingreasoning
    § Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125

    The hinge motion distorts the ATP-binding cleft of JNK1.

    “and distorts the ATPbinding cleft”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 6

  • May combine two claims.

    Findingown data
    § Interactions of the complex

    The Kd values for pepJIP1 binding to wild-type JNK1, R127A, and E329A are 0.42 ± 0.13, 6.4 ± 2.2, and 9.1 ± 3.4 μM, respectively.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Overall structure of JNK1 complexed with pepJIP1

    PepJIP1 docks to the docking groove of JNK1, a surface of the C-terminal domain covering alpha2, alpha3, alpha13, and beta8, which is away from the ATP pocket and substrate recognition site.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation
    § Introduction

    In the JNK1-pepJIP1 structure, the docking site of the scaffolding protein binds at the same docking grooves of JNK1 as the upstream kinase and substrate transcription factor do in p38 MAPK, but with different interaction modes.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Chang et al , 2002 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data
    § Disorder of the phosphorylation loop

    Much more residues of the phosphorylation loop of JNK1 complex are disordered than in JNK3 (missing residues 175-187 in JNK1-pepJIP1 and 212-216 in JNK3), although their ordered regions adopt a similar conformation.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Interdomain rearrangement mediated by pepJIP1 binding

    Binding of pepJIP1 to JNK1 rotates the N-terminal domain relative to the C-terminal domain by approximately 15°, distorting the ATP-binding site and inducing disorder of the phosphorylation loop.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    A key finding is that pepJIP1 binding causes interdomain rearrangement that distorts the ATP-binding site, offering an allosteric inhibition mechanism by blocking productive ATP binding.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Interdomain rearrangement mediated by pepJIP1 binding

    The hinge motion is triggered in beta8, which interacts with Leu162 by van der Waals contacts, and is propagated to the N-terminal domain via the single loop connecting beta7 and beta8.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § The ternary complex JNK1-pepJIP1-SP600125

    SP600125 occupied only the deepest adenine-binding site and did not expand to the phosphate-binding site in the ternary complex.

    “Fortunately, the small molecule, SP600125, occupied the deepest adenine-binding site only, not expanding to the phosphate-binding site”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § pepJIP1 as a JNK-specific inhibitor

    The fA-X-fB motif of pepJIP1, especially Leu162, is shifted relative to p38-bound peptides due to structural differences in the hydrophobic region, where JNK1 forms a one-turn helix alpha2 and p38 forms a two-turn helix.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Disorder of the phosphorylation loop

    In the JNK1-pepJIP1 complex, the alpha1 helix moved too far for interactions with the phosphorylation loop to occur, and this loss released the phosphorylation loop from the N-terminal domain, resulting in increased disorder.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Interdomain rearrangement mediated by pepJIP1 binding

    The r.m.s. deviations for Cα atoms of the N- and C-terminal domains between JNK1-pepJIP1 and JNK3 are 1.27 and 0.79 Å, respectively, showing no significant structural difference between corresponding domains.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Overexpression of JIP1 or its JNK-binding domain inhibits JNK signaling by retaining JNK in the cytoplasm and blocking its nuclear translocation.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dickens et al , 1997 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Introduction

    JIP1 is a scaffolding protein that assembles components of the JNK cascade and regulates JNK signaling.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Whitmarsh et al , 1998 source

      Not checked in the free run.

    • cites Dickens et al , 1997 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    In CDK6, INK4 inhibitors occupy a site adjacent to the ATP pocket, opposite the activating cyclin, and indirectly block cyclin binding while lowering ATP affinity through allosteric changes.

    “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.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Brotherton et al , 1998 source

      Not checked in the free run.

    • cites Russo et al , 1998 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § Disorder of the phosphorylation loop

    JNK and p38 may act as chemomechanical energy transducers, using peptide binding energy to generate allosteric conformational changes.

    “This implies that JNK and p38 may act as chemomechanical energy transducers, using peptide binding energy to generate allosteric conformational changes (Goldsmith, 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Goldsmith, 1996 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Each MAPK has similar yet nonidentical docking grooves, which may importantly determine pathway specificity alongside docking-site sequence differences.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Selectivity of SP600125 over other kinases

    Pocket size may relate to how flexible the loops near the catalytic cleft are in different kinases, and these flexibility differences could help determine SP600125 selectivity.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § The ternary complex JNK1-pepJIP1-SP600125

    SP600125 is a reversible inhibitor that competes with ATP and has over 20-fold selectivity for JNK over other kinases such as Erk, p38 MAPKs, MKKs, and PKCs.

    “SP600125 is a reversible ATPcompetitive inhibitor with more than 20-fold selectivity over other kinases including Erk, p38 MAPKs, MKKs, and PKCs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bennett et al , 2001 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § The ternary complex JNK1-pepJIP1-SP600125

    The structure of JNK3 in complex with SP600125 has been reported (PDB entry 1PMV).

    “Recently, the structure of JNK3 in complex with SP600125 was reported (PDB entry 1PMV; Scapin et al , 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Scapin et al , 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § The ternary complex JNK1-pepJIP1-SP600125

    In cells, SP600125 reduced c-jun phosphorylation and the expression of inflammatory genes (COX-2, IL2, IHNg, TNFa) in a dose-dependent way, and it prevented human CD4 cell activation and differentiation.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bennett et al , 2001 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Selectivity of SP600125 over other kinases

    A recent study found that SP600125 is not highly JNK-specific and that it blocks some protein kinases as strongly or more strongly than JNK.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bain et al , 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Interdomain rearrangement mediated by pepJIP1 binding

    The distortion would not eliminate ATP binding but would significantly reduce ATP affinity and may disorient bound ATP, inhibiting JNK activity to phosphorylate substrates.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Disorder of the phosphorylation loop

    Release of the phosphorylation loop when JNK binds JIP1 may allow the loop to refold and be recognized and phosphorylated by MKKs, and be ready to recognize substrates.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Conformational conservation of the / A-X-/ B motif

    The docking site can be characterized by both sequential similarity of the fA-X-fB motifs and conformational conservation of the motifs.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § The ternary complex JNK1-pepJIP1-SP600125

    In mice, SP600125 inhibited lipopolysaccharide-induced TNFa expression and prevented anti-CD3-mediated thymocyte apoptosis.

    “In in vivo studies in mice, SP600125 inhibited lipopolysaccharide-induced expression of TNFa and prevented anti-CD3-mediated thymocyte apoptosis (Bennett et al , 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bennett et al , 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning
    § Discussion

    Full-length JIP1 inhibition in vivo is more complex than pepJIP1 inhibition, and its structural basis may differ substantially from that of pepJIP1.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    JNK1's docking groove likely accepts MKK7 or c-jun docking sites as p38 does, but residues other than JIP1 Arg156 (fA4) may also be needed for specific MKK7 or c-jun recognition, since Arg156 is not conserved.

    “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).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning
    § Discussion

    MKK-mediated JNK phosphorylation and JNK-mediated c-jun activation may also involve interdomain rearrangement like that in the JNK1-pepJIP1 complex, owing to flexible loops near the catalytic cleft.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation
    § The ternary complex JNK1-pepJIP1-SP600125

    Blocking JNK therapeutically could be valuable for inflammatory disease, acute organ failure from apoptotic cell death, and cancer.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Interdomain rearrangement mediated by pepJIP1 binding

    The fact that the N- and C-terminal domains are linked by only two loops implies intrinsic flexibility may exist in the kinase, and this inherent structural flexibility may play a central role in its regulation upon JIP1 binding.

    “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.”
    Quote in the paperSubstantial claim
30 of 30

  • 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.”
2 of 2

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?

  • Both electrostatic pockets (W_L, W_U) are present and occupied by different KIM peptides in ERK, p38, and FUS3, while only the W_L pocket is engaged by KIM peptides that bind specifically to JNKs.

    “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]

    Heo et al. (2004) compares JIP1 peptide binding to JNK1 with peptide binding to p38 and discusses a JNK1-specific ionic interaction, but the passages found do not establish the claimed W_L/W_U comparison across ERK, p38, FUS3, and JNKs. Two paper-scoped Semantic Scholar searches returned no snippets. The wording appears almost verbatim in the same-topic review “Molecular basis of MAP kinase regulation” (score 0.906), but the available evidence does not establish that the review presents it independently of Heo et al.; misattribution is therefore not sufficiently supported. (LLM, conf=0.68)

    Experimental — accuracy not yet measured

  • The JNK1-pepNFAT4 and JNK1-pepJIP1 complexes adopted different main-chain conformations between the contact points corresponding to the D-motif consensus.

    “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]

    The ‘Overall structure of JNK1 complexed with pepJIP1’ section describes the pepJIP1 complex, but our copy does not describe a JNK1–pepNFAT4 complex. A search for NFAT4 found no comparison of the two peptides’ main-chain conformations. The ‘Conformational conservation of the φA–X–φB motif’ section compares pepJIP1 with other peptides, not pepNFAT4. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • Only three hydrophobic pockets (U_A, U_B, and U_L) are present in JNKs.

    “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]

  • The JNK1 structure bound to a JIP1 peptide showed peptide-induced rotation of the two lobes that distorted the active site, which was proposed to explain JIP1-mediated inhibition.

    “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

  • The original JIP1-bound JNK structure showed interlobe rotation but not the larger lobe opening or the allosteric signal transduction mechanism, because a single structure has limitations.

    “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

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.

  • The reported missing residues differ between sections

    Minor

    The disorder discussion identifies residues 175-187 as missing from the JNK1-pepJIP1 structure. The final model of that binary complex instead omits residues 173-189.

  • Figure 3 names different peptides for the blue labels

    Minor

    The Figure 3 caption identifies the blue peptide as pepMKK3b when describing the overlaid structures, but calls the blue-labeled residues pepMKK7 later in the same caption.

  • Figure 3 gives two numbers for the compared JNK1 glutamate

    Minor

    The text identifies the JNK1 residue compared with the corresponding JNK3 glutamate as Glu329, while the Figure 3 caption calls it E327.

3 of 3

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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
Publisher
Springer Science and Business Media LLC
Published
2004-05-13
Volume
23
Issue
11
Pages
2185-2195
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1038/sj.emboj.7600212
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
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

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