Cited by 1,555Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

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Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

Dérijard, Benoit, Raingeaud, Joël, Barrett, Tamera, Wu, I-Huan, Han, Jiahuai, Ulevitch, Richard J., Davis, Roger J.·1995·Science

DOI 10.1126/science.7839144

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Abstract

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.

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Background
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BackgroundInfluential
Discordant Activation of Stress-activated Protein Kinases or c-Jun NH2-terminal Protein Kinases in Tissues of Heat-stressed Mice
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“The kinase reaction was performed with 50 mM HEPES (pH 7.4)–10 mM MgCl2–20 mM ATP– [g-32P]ATP containing 5 mg of GST-SEK1 K-R mutant [SEK1 (K-R)] for 5 min at 30°C. Chelerythrine chloride (200 mM; Sigma) was added as needed.”
Influential
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Self-citation
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“…dual specificity MAP2Ks (JNKK1/MKK4/SEK1 and JNKK2/MKK7) is required for its full activation by various extracellular stimuli (Sanchez et al., 1994; Derijard et al., 1995; Lin et al., Annning Lin would like to dedicate this review in memory of his father, Jun Lin, who passed away due to heart…”
Background
Induction of Cytosolic Phospholipase A2 by Oncogenic Ras Is Mediated through the JNK and ERK Pathways in Rat Epithelial Cells
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Activation of p38MAPK mediates the angiostatic effect of the chemokine receptor CXCR3-B
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BackgroundInfluential
Transforming Growth Factor-β1 Suppresses Serum Deprivation-induced Death of A549 Cells through Differential Effects on c-Jun and JNK Activities
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“Two different upstream kinases, MKK3 and MKK6, activate p38 (24, 38, 75, 79, 95, 110, 127).”
Background
Role of reactive oxygen species in cells overexpressing manganese superoxide dismutase: mechanism for induction of radioresistance.
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Self-citation
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“two MAPKs that are reported to selectively phosphorylate and activate p38 (10, 22, 23).”
Background
Phosphorylation of Bad at Thr-201 by JNK1 Promotes Glycolysis through Activation of Phosphofructokinase-1
Deng, H., Yu, F., Chen, J., Zhao, Y., Xiang, J., & Lin, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800024200 · Cited by 67
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“A SAPK cascade results in the phosphorylation and activation of MAP2K4, which in turn activates Jun kinases (JNK1-3) and the p38 protein, which are MAPK homologs (Sanchez et al., 1994; Derijard et al., 1995; Lin et al., 1995).”
Background
Cyclic AMP Inhibits p38 Activation via CREB-Induced Dynein Light Chain
Zhang, J., Bui, T. N., Xiang, J., & Lin, A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.4.1223-1234.2006 · Cited by 64
“Immunoblotting analysis revealed that the phosphorylation of MKK3/6, which are major MAP2Ks for p38 in cells (5, 12 , 24), was not affected (Fig. 5E and F). Similar results were obtained with FL5.12 cells, in which pretreatment with forskolin had no effects on IL-3-induced phosphorylation of MKK3/6 (Fig. 5G).”
BackgroundResultInfluential
Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules
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Background
Inhibition of extracellular signal-regulated kinase (ERK) mediates cell cycle phase independent apoptosis in vinblastine-treated ML-1 cells.
Stadheim, T. A., Xiao, H., & Eastman, A. R. (2001) · PubMed · Cited by 64
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“Recombinants were screened for the correct orientation and sequenced. pGFP-Net(L16A), pTL2-Net(L16A), pGFP-N5Dm, pGFP-NetDm, and pGFP-NetDelk were constructed by double-round PCR mutagenesis and sequenced. pTL2-Net encodes mouse Net (16). pTL1-Elk1 encodes human Elk1 (16). pKOZ1-Sap1a encodes human Sap1a (44). pRasCTB…”
BackgroundInfluential
Cellular activation mechanisms in septic shock
Han, J. (1998) · Frontiers in bioscience · doi:10.2741/a293 · Cited by 64
Self-citation
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Ceresa, B. P., Horvath, C. M., & Pessin, J. E. (1997) · Endocrinology · doi:10.1210/endo.138.10.5266 · Cited by 64
PKC δ mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells
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“ERK is activated mainly by tyrosine kinase-encoded receptors and G proteincoupled receptors that induce mitogenesis and di erentiation (Cobb and Goldsmith, 1995; Marshall, 1995), whereas the JNK and p38 MAPK subgroups are Oncogene (2001) 20, 989 ± 996 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $…”
BackgroundMethodInfluential
The Stress Kinase Mitogen-Activated Protein Kinase Kinase (Mkk)7 Is a Negative Regulator of Antigen Receptor and Growth Factor Receptor–Induced Proliferation in Hematopoietic Cells
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Constitutively active mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 mediate similar transcriptional and morphological responses.
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jkk‐1 and mek‐1 regulate body movement coordination and response to heavy metals through jnk‐1 in Caenorhabditis elegans
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“While MKK4 also functions as an activator of p38, MKK7 probably functions as a specific activator of JNK (Cavigelli et al., 1995; Derijard et al., 1995; Tournier et al., 1997).”
Background
The GABP-responsive Element of the Interleukin-2 Enhancer Is Regulated by JNK/SAPK-activating Pathways in T Lymphocytes
Hoffmeyer, A., Avots, A., Flory, E., Weber, C. K., Serfling, E., & Rapp, U. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.17.10112 · Cited by 63
Mechanism of UV-Induced Apoptosis in Human Leukemia Cells: Roles of Ca2+/Mg2+-Dependent Endonuclease, Caspase-3, and Stress-Activated Protein Kinases
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Improved HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma
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Identification of a Novel Amino Acid Response Pathway Triggering ATF2 Phosphorylation in Mammals
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“specificity of a signaling pathway (22).”
Self-citation
Nicotine affects the signaling of the death pathway, reducing the response of head and neck cancer cell lines to DNA damaging agents
Onoda, N., Nehmi, A., Weiner, D. E., Mujumdar, S., Christen, R. D., & Los, G. (2001) · Head & Neck · doi:10.1002/hed.1125 · Cited by 62
“The immune complexes were then assayed for kinase activity using GST-c-Jun (79) as a substrate.25 Using this approach, a low level of GST-Jun phosphorylation was detectable in the anti-JNK1 immunoprecipitates obtained from untreated cells (Fig.”
MethodInfluential
Up‐regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia
Lotan, T., Lyon, M. B., Huo, D., Taxy, J., Brendler, C. B., Ba, F., Stadler, W. M., & Rinker-Schaeffer, C. W. (2007) · The Journal of Pathology · doi:10.1002/path.2194 · Cited by 62
Asymmetric p38 Activation in Zebrafish
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“A fragment encoding three tandem repeats of hemagglutinin epitopes was excised from pSR a - HA-JNK1 (Derijard et al., 1995) and fused to the MKK3 cDNA followed by subcloning into the pCS2 1 expression vector.”
Method
Enhancement of p38 Mitogen-activated Protein Kinase Activity by Phosphorylated Glia Maturation Factor
Lim, R., & Zaheer, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.38.22953 · Cited by 62
MEKK2 Is Required for T-cell Receptor Signals in JNK Activation and Interleukin-2 Gene Expression
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Cellular Responses to Tumor Necrosis Factor
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“It is known that the upstream MAP kinase kinases of p38α are MKK3 (or MEK3) and MKK6 (or MEK6) (Derijard et al., 1995; Han et al., 1996).”
BackgroundSelf-citation
Role of ATM in Oxidative Stress-mediated c-Jun Phosphorylation in Response to Ionizing Radiation and CdCl2
Lee, S. A., Dritschilo, A., & Jung, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004517200 · Cited by 62
Identification and characterization of a predominant isoform of human MKK3
Han, J., Wang, X., Jiang, Y., Ulevitch, R. J., & Lin, S. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00021-5 · Cited by 62
Self-citation
Differential calcium dependence in the activation of c-Jun kinase and mitogen-activated protein kinase by muscarinic acetylcholine receptors in rat 1a cells
Mitchell, F. M., Russell, M., & Johnson, G. L. (1995) · Biochemical Journal · doi:10.1042/bj3090381 · Cited by 62
TNF-α mediates pseudorabies virus-induced apoptosis via the activation of p38 MAPK and JNK/SAPK signaling
Yeh, C.-J., Lin, P., Liao, M., Liu, H., Lee, J., Chiu, S.-J., Hsu, H., & Shih, W. (2008) · Virology · doi:10.1016/j.virol.2008.08.023 · Cited by 61
“Activation of MAPK and MAPKK occurs via phosphorylation of certain amino acids (Derijard et al.,1994; Derijard et al.,1995; Pulverer et al.,1991; Smeal et al.,1991).”
Background
PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: Involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways
Castorina, A., Scuderi, S., D’Amico, A. G., Drago, F., & D’Agata, V. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.11.003 · Cited by 61
“MAPKK or MEK1) activity [10], both in serum starved and 10% FBS cultured schwannoma cells supplemented or not with either 100 nM PACAP or VIP.”
Background
cFLIP-L Inhibits p38 MAPK Activation
Grambihler, A., Higuchi, H., Bronk, S. F., & Gores, G. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303229200 · Cited by 61
Activation of Cardiac c-Jun NH 2 -Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load
Fischer, T. A., Ludwig, S., Flory, E., Gambaryan, S. P., Singh, K., Finn, P. V., Pfeffer, M. A., Kelly, R. A., & Pfeffer, J. M. (2001) · Hypertension · doi:10.1161/01.hyp.37.5.1222 · Cited by 61
“The pGEX-KG-c-Jun(1135) vector for expression of GST-c-Jun(1-135) was a kind gift from J. Kyriakis and L. Zon (Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charleston).”
MethodInfluential
Cell adhesion differentially regulates the nucleocytoplasmic distribution of active MAP kinases
Aplin, A. E., Hogan, B. P., Tomeu, J., & Juliano, R. L. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.13.2781 · Cited by 61
JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer's disease
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“JKK1 mRNA is widely expressed in human tissue, but is especially abundant in skeletal muscle and brain (Sanchez et al. 1994; Derijard et al. 1995).”
Background
p21-activated Protein Kinase γ-PAK Is Translocated and Activated in Response to Hyperosmolarity
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CD40-CD154 Interactions in B-Cell Signaling
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The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway
He, F., Xiao, Z., Yao, H., Li, S., Feng, M., Wang, W., Liu, Z., Liu, Z., & Wu, J. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-2077-y · Cited by 60
Targeting MKK3 as a novel anticancer strategy: molecular mechanisms and therapeutical implications
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TLR and TNF-R1 activation of the MKK3/MKK6–p38α axis in macrophages is mediated by TPL-2 kinase
Pattison, M. J., Mitchell, O., Flynn, H. R., Chen, C.-S., Yang, H., Ben-Addi, H., Boeing, S., Snijders, A. P., & Ley, S. C. (2016) · Biochemical Journal · doi:10.1042/bcj20160502 · Cited by 61
Signaling events controlling the molecular response to genotoxic stress
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Transforming growth factor-β1-induced endothelial barrier dysfunction involves Smad2-dependent p38 activation and subsequent RhoA activation
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INVOLVEMENT OF p38 AND JNK MAPKs PATHWAYS IN SUBSTANCE P-INDUCED PRODUCTION OF TNF-α BY PERITONEAL MAST CELLS
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Activation of Human Neutrophils by Mycobacterium tuberculosis H37Ra Involves Phospholipase Cγ2, Shc Adapter Protein, and p38 Mitogen-Activated Protein Kinase
Perskvist, N., Zheng, L., & Stendahl, O. I. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.2.959 · Cited by 59
Cyclic AMP Inhibition of Thrombin-induced Growth in Vascular Smooth Muscle Cells Correlates with Decreased JNK1 Activity and c-Jun Expression
Rao, G. N., & Runge, M. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20805 · Cited by 60
Coordinated Regulation of Radioadaptive Response by Protein Kinase C and p38 Mitogen-Activated Protein Kinase
Shimizu, T., Kato, T., Tachibana, A., & Sasaki, M. S. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4582 · Cited by 73
MLK3 Is Part of a Feedback Mechanism That Regulates Different Cellular Responses to Reactive Oxygen Species
Lee, H.-S., Hwang, C. Y., Shin, S., Kwon, K., & Cho, K. (2014) · Science Signaling · doi:10.1126/scisignal.2005260 · Cited by 62
Developmental Regulation of Mitogen-Activated Protein Kinase-Activated Kinases-2 and -3 (MAPKAPK-2/-3) in Vivo during Corpus Luteum Formation in the Rat
Maizels, E. T., Mukherjee, A., Sithanandam, G., Peters, C. A., Cottom, J. E., Mayo, K. E., & Hunzicker-Dunn, M. E. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.5.0634 · Cited by 59
“The following were purchased from indicated vendors or kindly provided by indicated colleagues: MAPKAPK-2 antibody, StressGen Biotechnology (Victoria, British Columbia, Canada); HSP-27 monoclonal antibody, Dr. Michael Welsh, University of Michigan, Ann Arbor, MI (83); phospho-specific p38 MAPK (T180,Y182) and monoclon…”
BackgroundInfluential
Convergence of CpG DNA- and BCR-mediated signals at the c-Jun N-terminal kinase and NF-kappaB activation pathways: regulation by mitogen-activated protein kinases
Yi, A. (2003) · International Immunology · doi:10.1093/intimm/dxg058 · Cited by 59
Chemotactic Peptide-induced Activation of MEK-2, the Predominant Isoform in Human Neutrophils
Downey, G. P., Butler, J. R., Brumell, J. H., Borregaard, N., Kjeldsen, L., Sue‐A‐Quan, A. K., & Grinstein, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21005 · Cited by 59
“Three families of MAP kinases have been described: the ERKs, c-Jun NH2-terminal kinase (JNK or SAPK) and p38 (Derijard et al., 1995).”
Method
Cutaneous innate immune tolerance is mediated by epigenetic control of MAP2K3 by HDAC8/9
Sawada, Y., Nakatsuji, T., Dokoshi, T., Kulkarni, N. N., Liggins, M. C., Sen, G., & Gallo, R. L. (2021) · Science Immunology · doi:10.1126/sciimmunol.abe1935 · Cited by 58
Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin‐6 expression through multiple mitogen‐activated protein kinase pathways in periodontal ligament fibroblasts
Patil, C., Rossa, C., & Kirkwood, K. L. (2006) · Oral Microbiology and Immunology · doi:10.1111/j.1399-302x.2006.00314.x · Cited by 58
“isoforms of both MKK-3 and -6 have been shown to have reduced kinase activity on p38a MAPK substrates (4).”
Background
Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway
Zhu, Y., Gu, Y., Jiang, C., & Chen, L. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29131 · Cited by 58
“…receptor 2 that can activate P38 (Ge et al., 2016); in addition, MKK3 and MKK6 are the upstream protein kinases responsible for p38 activation (Dérijard et al., 1995; Remy et al., 2010), the MKK3/6‐p38 pathway has been suggested as the main mediator of TGF‐b‐activated kinase 1 in…”
Background
Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IκB kinases (IKK-α/β) and IKK-β is a developmentally regulated protein kinase
Hu, M. C. ‐., Wang, Y.-P., Qiu, W. R., Mikhail, A. A., Meyer, C. F., & Tan, T. (1999) · Oncogene · doi:10.1038/sj.onc.1202740 · Cited by 58
“…is a critical regulator of the c-Jun amino-terminal kinases (JNKs)/stress-activated protein kinases (SAPKs) (Minden et al., 1994; Yan et al., 1994; Derijard et al., 1995) and hematopoietic progenitor kinase-1 (HPK1) is an upstream activator of MEKK1 (Hu et al., 1996), thereby raising the…”
Background
A β-Catenin-Independent Dorsalization Pathway Activated by Axin/JNK Signaling and Antagonized by Aida
Rui, Y., Xu, Z., Xiong, B., Cao, Y., Lin, S., Zhang, M., Chan, S.-C., Luo, W., Han, Y., Ye, Z., et al. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.006 · Cited by 58
Self-citation
Activation of the ras-mitogen-activated protein kinase pathway and phosphorylation of ets-2 at position threonine 72 in human ovarian cancer cell lines.
Patton, S. E., Martin, M. L., Nelsen, L., Fang, X., Mills, G. B., Bast, R. C., & Ostrowski, M. C. (1998) · PubMed · Cited by 58
Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines
Mielke, K., Damm, A., Yang, D. D., & Herdegen, T. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00308-3 · Cited by 58
Oleic Acid and Angiotensin II Induce a Synergistic Mitogenic Response in Vascular Smooth Muscle Cells
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Vitamin E down-modulates mitogen-activated protein kinases, nuclear factor-κB and inflammatory responses in lung epithelial cells
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Inhibitors of p38 Mitogen-Activated Protein Kinase
Newton, R. C., & Holden, N. S. (2003) · BioDrugs · doi:10.2165/00063030-200317020-00004 · Cited by 57
p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion
Hayes, S. A., Huang, X., Kambhampati, S., Platanias, L. C., & Bergan, R. C. (2003) · Oncogene · doi:10.1038/sj.onc.1206730 · Cited by 57
“The dominantnegative p38 expression plasmid pCMV5-p38AGF was obtained from Roger Davis (University of Massachusetts, Worcester, MA, USA) and has been previously described (Derijard et al., 1995).”
Method
UV Irradiation Induces the Murine Urokinase-Type Plasminogen Activator Gene via the c-Jun N-Terminal Kinase Signaling Pathway: Requirement of an AP1 Enhancer Element
Miralles, F., Parra, M., Caelles, C., Nagamine, Y., Félez, J., & Muñoz‐Cánoves, P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4537 · Cited by 57
“The third MAPK subfamily, p38 (also known as CSBP, RK, Mxi2, and SAPK2a), is a homolog of the yeast MAPK Hog-1 (highosmolarity glycerol response 1) kinase (35, 51, 75, 90) and is phosphorylated and activated by MEK family member MKK3 (24).”
Background
miR-92a inhibits vascular smooth muscle cell apoptosis: role of the MKK4–JNK pathway
Zhang, L., Zhou, M., Wang, Y., Huang, W., Qin, G., Weintraub, N. L., & Tang, Y. (2014) · APOPTOSIS · doi:10.1007/s10495-014-0987-y · Cited by 56
“For MKK4 overexpression experiments, VSMC were transfected with pCDNA3 FlagMKK4 (Addgene 14615) plasmid [18].”
Toll-like receptor signalling pathways as key targets for mediating the anti-inflammatory and immunosuppressive effects of glucocorticoids
Moynagh, P. N. (2003) · Journal of Endocrinology · doi:10.1677/joe.0.1790139 · Cited by 56
“Thus IL-1 and LPS induce phosphorylation of p38, ERK1/2 and JNK (Freshney et al. 1994, Rouse et al. 1994, Derijard et al. 1995, Lin et al. 1995, Ulevitch & Tobias 1995).”
Background
Hck Is a Key Regulator of Gene Expression in Alternatively Activated Human Monocytes
Bhattacharjee, A., Pal, S., Feldman, G. M., & Cathcart, M. K. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.291492 · Cited by 56
Salidroside represses proliferation, migration and invasion of human lung cancer cells through AKT and MEK/ERK signal pathway
Ren, M., Xu, W., & Xu, T. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1584566 · Cited by 58
“Mitogen-activated protein kinase (MAPKK, also known as MEK) is a kinase enzyme which phosphorylates mitogenactivated protein kinase (MAPK, also known as ERK) [39].”
Background
Nitroxides Tempol and Tempo Induce Divergent Signal Transduction Pathways in MDA-MB 231 Breast Cancer Cells
Suy, S., Mitchell, J. B., Ehleiter, D., Haimovitz‐Friedman, A., & Kasid, U. N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17871 · Cited by 56
LPS-Induced NF-κB Activation and TNF-α Release in Human Monocytes Are Protein Tyrosine Kinase Dependent and Protein Kinase C Independent
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Bisindolylmaleimide VIII Enhances DR5-mediated Apoptosis through the MKK4/JNK/p38 Kinase and the Mitochondrial Pathways
Ohtsuka, T., & Zhou, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203342200 · Cited by 56
Differential activation of T cell cytokine production by the extracellular signal‐regulated kinase (ERK) signaling pathway
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Differential expression of active, phosphorylation-dependent MAP kinases, MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates following quinolinic acid excitotoxicity in the rat
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Authors: Dérijard, B., Raingeaud, J., Barrett, T., Wu, I.-H., Han, J., Ulevitch, R. J., & Davis, R. J.
Affiliations: University of Massachusetts Chan Medical School (US)
ORCID: Han, Jiahuai
Ulevitch, Richard J.
Davis, Roger J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1995-02-03
Volume: 267
Issue: 5198
Pages: 682-685
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7839144
OpenAlex: W1998487776
Cited by: 1,555
References: 29
Citations by year: 2026: 8 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 16 · 2021: 19 · 2020: 14 · 2019: 20 · 2018: 16 · 2017: 19 · 2016: 24 · 2015: 15 · 2014: 27 · 2013: 25 · 2012: 27
FWCI: 53.10
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca058396-09)
National Cancer Institute (CA 58396)
National Institute of General Medical Sciences (GM 37696, P01GM037696)
National Institute of Allergy and Infectious Diseases (AI 15136, R01AI015136)
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 › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: MAPK signaling, MKK3, MKK4, p38 MAPK, ERK, JNK, signaling pathways, dual phosphorylation
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Substrate Specificity, Transfection, Signal Transduction, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 3, MAP Kinase Kinase 4

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Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

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