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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Site-directed mutagenesis by overlap extension using the polymerase chain reaction
Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90358-2 · Cited by 7,414
Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase
Smith, D. B., & Johnson, K. S. (1988) · Gene · doi:10.1016/0378-1119(88)90005-4 · Cited by 5,844
JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J. (1994) · Cell · doi:10.1016/0092-8674(94)90380-8 · Cited by 3,188
Self-citation
A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells
Han, J., Lee, J. D., Bibbs, L., & Ulevitch, R. J. (1994) · Science · doi:10.1126/science.7914033 · Cited by 2,647
Self-citation
The stress-activated protein kinase subfamily of c-Jun kinases
Kyriakis, J. M., Banerjee, P. T., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., & Woodgett, J. R. (1994) · Nature · doi:10.1038/369156a0 · Cited by 2,601
The mitogen-activated protein kinase signal transduction pathway
Davis, R. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82362-6 · Cited by 2,112
Self-citation
A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins
Rouse, J. W., Cohen, P., Trigon, S., Morange, M., Alonso‐Llamazares, A., Zamanillo, D., Hunt, T., & Nebreda, Á. R. (1994) · Cell · doi:10.1016/0092-8674(94)90277-1 · Cited by 1,671
Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway
Gupta, S., Campbell, D., Dérijard, B., & Davis, R. J. (1995) · Science · doi:10.1126/science.7824938 · Cited by 1,433
Self-citation
An Osmosensing Signal Transduction Pathway in Yeast
Brewster, J. L., de Valoir, T., Dwyer, N. D., Winter, E., & Gustin, M. C. (1993) · Science · doi:10.1126/science.7681220 · Cited by 1,248
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme
Andersson, S., Davis, D. L., Dahlbäck, H., Jörnvall, H., & Russell, D. W. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83172-6 · Cited by 1,229

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DRESSLER, H, BIOTECHNIQUES 13: 866 (1992).

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Items 201–300 of 999

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Schwenger, P., Bellosta, P., Vietor, I., Basilico, C., Skolnik, E. Y., & Vilček, J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.2869 · Cited by 273
Inhibition of UVB-Induced Oxidative Stress-Mediated Phosphorylation of Mitogen-Activated Protein Kinase Signaling Pathways in Cultured Human Epidermal Keratinocytes by Green Tea Polyphenol (−)-Epigallocatechin-3-gallate
Katiyar, S. K., Afaq, F., Azizuddin, K., & Mukhtar, H. (2001) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2001.9276 · Cited by 272
Induction of Cyclooxygenase-2 by the Activated MEKK1 → SEK1/MKK4 → p38 Mitogen-activated Protein Kinase Pathway
Guan, Z., Buckman, S. Y., Pentland, A. P., Templeton, D. J., & Morrison, A. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12901 · Cited by 271
Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH 2 -terminal kinase activation, and defects in AP-1 transcriptional activity
Yang, D., Tournier, C., Wysk, M., Lu, H., Xu, J., Davis, R. J., & Flavell, R. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.3004 · Cited by 271
Self-citation
Modulation of actin dynamics during stress and physiological stimulation by a signaling pathway involving p38 MAP kinase and heat-shock protein 27
Landry, J., & Huot, J. (1995) · Biochemistry and Cell Biology · doi:10.1139/o95-078 · Cited by 269
Tumor Necrosis Factor Signaling to Stress-activated Protein Kinase (SAPK)/Jun NH2-terminal Kinase (JNK) and p38
Yuasa, T., Ohno, S., Kehrl, J. H., & Kyriakis, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.35.22681 · Cited by 268
Deficiency of the Stress Kinase P38α Results in Embryonic Lethality
Allen, M. R., Svensson, L., Roach, M. L., Hambor, J., McNeish, J. D., & Gabel, C. A. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.859 · Cited by 268
“For example, p38a was efficiently activated by MKK3, MKK4, or MKK6 in transfected COS-7 cells, whereas p38b was phosphorylated only by MKK6 (20).”
Background
The 70 kDa S6 Kinase Complexes with and Is Activated by the Rho Family G Proteins Cdc42 and Rac1
Chou, M. M., & Blenis, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81257-x · Cited by 292
Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta.
Berra, E., Díaz-Meco, M. T., Lozano, J., Frutos, S., Municio, M. M., Sánchez‐Gómez, P., Sanz, L., & Moscat, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00306.x · Cited by 263
Crystal Structure of p38 Mitogen-activated Protein Kinase
Wilson, K. P., Fitzgibbon, M. J., Caron, P. R., Griffith, J. P., Chen, W., McCaffrey, P. G., Chambers, S. P., & Su, M. S. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27696 · Cited by 262
Activation of a Novel Calcium-dependent Protein-tyrosine Kinase
Yu, H., Li, X., Marchetto, G. S., Dy, R. C., Hunter, D., Calvo, B. F., Dawson, T. L., Wilm, M. S., Anderegg, R. J., Graves, L. M., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.29993 · Cited by 264
Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy
Steelman, L. S., Franklin, R. A., Abrams, S. L., Chappell, W. H., Kempf, C., Bäsecke, J., Stivala, F., Donia, M., Fagone, P., Nicoletti, F., et al. (2011) · Leukemia · doi:10.1038/leu.2011.66 · Cited by 271
MEK and the inhibitors: from bench to bedside
Akinleye, A., Furqan, M., Mukhi, N., Ravella, P., & Liu, D. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-27 · Cited by 291
“MEK4, in addition to its principal target, JNK, also crosstalks with MEK3/6-p38MAPK pathway by activating p38α and p38β [41-43].”
Mitochondrial Reactive Oxygen Species Activation of p38 Mitogen-Activated Protein Kinase Is Required for Hypoxia Signaling
Emerling, B. M., Platanias, L. C., Black, E. V. I., Nebreda, Á. R., Davis, R. J., & Chandel, N. S. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.4853-4862.2005 · Cited by 259
“MKK3 and MKK6 are the upstream MAPKK isoforms that specifically activate p38 MAPK (5, 10, 37).”
BackgroundSelf-citation
NIK is a new Ste20‐related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain
Su, Y. C., Han, J., Xu, S., Cobb, M. H., & Skolnik, E. Y. (1997) · The EMBO Journal · doi:10.1093/emboj/16.6.1279 · Cited by 256
“…Several distinct MAP kinase modules have been identified in yeast and mammalian cells (Minden et al., 1994;aspartic acid at position 152 was mutated to asparagine [NIK(D152N)] was also transiently expressed in 293 Sanchez et al., 1994; Yan et al., 1994; Derijard et al., 1995; Herskowitz, 1995).”
BackgroundSelf-citation
Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade.Preprint
Hu, M. C. ‐., Qiu, W., Wang, X., Meyer, C. F., & Tan, T. (1996) · Genes & Development · doi:10.1101/gad.10.18.2251 · Cited by 255
A novel SAPK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses
Moriguchi, T., Toyoshima, F., Masuyama, N., Hanafusa, H., Gotoh, Y., & Nishida, E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.23.7045 · Cited by 250
“Specific activators for p38, MKK3 and MKK6, have been described (Derijard et al., 1995; Han et al., 1996; Moriguchi et al., 1996a; Raingeaud et al., 1996; Stein et al., 1996) and, for SAPK/JNK, SEK1/MKK4 has been identified as a direct activator (Sanchez et al.”
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Wang, X., McGowan, C. H., Zhao, M. F., He, L., Downey, J. S., Fearns, C., Wang, Y., Huang, S., & Han, J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.13.4543-4552.2000 · Cited by 247
“Two MAP kinase kinases, MKK3 and MKK6, have been identified as immediate upstream activators of the p38 family (13).”
BackgroundMethodInfluentialSelf-citation
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Lee, J. T., & McCubrey, J. A. (2002) · Leukemia · doi:10.1038/sj.leu.2402460 · Cited by 250
Expression of mitogen-inducible cyclooxygenase induced by lipopolysaccharide
Hwang, D. H., Jang, B. C., Yu, G., & Boudreau, M. D. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00154-8 · Cited by 248
T Cell Proliferation in Response to Interleukins 2 and 7 Requires p38MAP Kinase Activation
Crawley, J. B., Rawlinson, L. M., Lali, F. V., Page, T. H., Saklatvala, J., & Foxwell, B. M. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.23.15023 · Cited by 245
UVB Activates ERK1/2 and p38 Signaling Pathways via Reactive Oxygen Species in Cultured Keratinocytes
Péus, D., Vasa, R. A., Beyerle, A., Meves, A., Krautmacher, C., & Pittelkow, M. R. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00584.x · Cited by 244
“Epidermal growth factor (EGF) and phorbol esters have been reported to be poor activators of p38 (Derijard et al, 1995; Rouse et al, 1994).”
Background
The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways
Lu, X., Nguyen, T., Moon, S.-H., Darlington, Y. F., Sommer, M., & Donehower, L. A. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9127-x · Cited by 251
“Genotoxic stress such as UV radiation causes activation of p38 MAP kinase by dual phosphorylation on Thr180 and Tyr182 [32, 33].”
Background
HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway.
Kiefer, F., Tibbles, L. A., Anafi, M., Janssen, A., Zanke, B. W., Lassam, N. J., Pawson, T. J., Woodgett, J. R., & Iscove, N. N. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01093.x · Cited by 242
Cloning of a Novel Mitogen-activated Protein Kinase Kinase Kinase, MEKK4, That Selectively Regulates the c-Jun Amino Terminal Kinase Pathway
Gerwins, P., Jonathan, L., & Johnson, G. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8288 · Cited by 242
The Role of Mitophagy in Innate Immunity
Gkikas, I., Palikaras, K., & Tavernarakis, N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01283 · Cited by 248
“Notably, MKK3 stimulates p38 MAP kinase signaling to promote septic shock (146, 147).”
Background
Molecular Mechanisms of c-Jun N-terminal Kinase-mediated Apoptosis Induced by Anticarcinogenic Isothiocyanates
Chen, Y., Wang, W., Kong, A.-N. T., & Tan, T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.3.1769 · Cited by 238
A non-enzymatic p21 protein inhibitor of stress-activated protein kinases
Shim, J., Lee, H.-J., Park, J., Kim, H., & Choi, E. (1996) · Nature · doi:10.1038/381804a0 · Cited by 236
Endothelial Cell Inflammatory Responses to Tumor Necrosis Factor α
Modur, V., Zimmerman, G. A., Prescott, S. M., & McIntyre, T. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13094 · Cited by 234
AMP-activated Protein Kinase and p38 MAPK Activate O-GlcNAcylation of Neuronal Proteins during Glucose Deprivation
Cheung, W. D., & Hart, G. W. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801222200 · Cited by 248
MPTP Activates c‐Jun NH2‐Terminal Kinase (JNK) and Its Upstream Regulatory Kinase MKK4 in Nigrostriatal Neurons In Vivo
Saporito, M. S., Thomas, B. A., & Scott, R. W. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751200.x · Cited by 233
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Background
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Guan, Z., Buckman, S. Y., Miller, B. W., Springer, L. D., & Morrison, A. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28670 · Cited by 233
Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression
Bruder, J. T., & Kovesdi, I. (1997) · Journal of Virology · doi:10.1128/jvi.71.1.398-404.1997 · Cited by 230
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Background
Independent regulation of JNK/p38 mitogen-activated protein kinases by metabolic oxidative stress in the liver
Mendelson, K. G., Contois, L. W., Tevosian, S. G., Davis, R. J., & Paulson, K. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12908 · Cited by 232
Self-citation
ATF3 Gene
Liang, G., Wolfgang, C. D., Chen, B. P. C., Chen, T.-H., & Hai, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1695 · Cited by 231
Repression of human heat shock factor 1 activity at control temperature by phosphorylation.Preprint
Knauf, U., Newton, E. M., Kyriakis, J. M., & Kingston, R. E. (1996) · Genes & Development · doi:10.1101/gad.10.21.2782 · Cited by 231
“…well understood than the ERK pathway; however, SAPK is believed to be activated by a MEK equivalent called SEKI(JNKK1)(MKK4) (Sanchez et al. 1994; Derijard et al. 1995; Lin et al. 1995), which appears itself to be regulated by MEKK (MAP kinase kinase kinase) (Lange-Carter et al. 1993; Yan et al.…”
Background
Protein kinases of the Hippo pathway: Regulation and substrates
Avruch, J., Zhou, D., Fitamant, J., Bardeesy, N. M., Mou, F., & Regué, L. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.07.002 · Cited by 231
“[74] Dérijard B, Raingeaud J, Barrett T, Wu IH, Han J, Ulevitch RJ, et al.”
Background
Opposing Effects of Jun Kinase and p38 Mitogen-Activated Protein Kinases on Cardiomyocyte Hypertrophy
Nemoto, S., Sheng, Z., & Lin, A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3518 · Cited by 230
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Blank, J. L., Gerwins, P., Elliott, E. M., Sather, S., & Johnson, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5361 · Cited by 230
c-Jun N-Terminal Kinase Phosphorylates Peroxisome Proliferator-Activated Receptor- 1 and Negatively Regulates Its Transcriptional Activity
Camp, H. S., Tafuri, S. R., & Leff, T. (1999) · Endocrinology · doi:10.1210/endo.140.1.6457 · Cited by 235
Mitogen-activated protein kinases
Arbabi, S., & Maier, R. V. (2002) · Critical Care Medicine · doi:10.1097/00003246-200201001-00010 · Cited by 232
The architecture of the interleukin-2 promoter: a reflection of T lymphocyte activation
Serfling, E., Avots, A., & Neumann, M. (1995) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(95)00112-t · Cited by 229
5-HT1A receptor-regulated signal transduction pathways in brain
Polter, A. M., & Li, X. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.03.019 · Cited by 225
p38 Pathway Kinases as Anti-inflammatory Drug Targets
Schindler, J. F., Monahan, J. B., & Smith, W. G. (2007) · Journal of Dental Research · doi:10.1177/154405910708600902 · Cited by 232
“The protein kinases MKK3 and MKK6 specifically activate the p38 MAPKs (Derijard et al., 1995).”
Influential
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Background
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Razandi, M., Pedram, A., & Levin, E. R. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.9.0526 · Cited by 228
“be defined in a situation-specific context (59).”
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Choi, W.-S., Eom, D. S., Han, B., Kim, W. K., Han, B. H., Choi, E., Oh, T. H., Markelonis, G. J., Cho, J. W., & Oh, Y. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311164200 · Cited by 227
Activation of the p38 Mitogen-activated Protein Kinase by Type I Interferons
Shahab Uddin, M. S., Majchrzak, B., Woodson, J., Arunkumar, P., Alsayed, Y. M., Pine, R. I., Young, P. R., Fish, E. N., & Platanias, L. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.30127 · Cited by 227
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Huang, S., Jiang, Y., Li, Z., Nishida, E., Mathias, P., Lin, S., Ulevitch, R. J., Nemerow, G. R., & Han, J. (1997) · Immunity · doi:10.1016/s1074-7613(00)80449-5 · Cited by 227
Self-citation
Serine Phosphorylation and Negative Regulation of Stat3 by JNK
Lim, C. P., & Cao, X. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.31055 · Cited by 225
Coordinate Regulation of IκB Kinases by Mitogen-Activated Protein Kinase Kinase Kinase 1 and NF-κB-Inducing Kinase
Nemoto, S., DiDonato, J. A., & Lin, A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.7336 · Cited by 224
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BackgroundInfluential
The Mixed Lineage Kinase SPRK Phosphorylates and Activates the Stress-activated Protein Kinase Activator, SEK-1
Rana, A., Gallo, K. A., Godowski, P. J., Hirai, S.-I., Ohno, S., Zon, L. I., Kyriakis, J. M., & Avruch, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19025 · Cited by 223
The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesisPreprint
Mayer, C., Bierhoff, H., & Grummt, I. (2005) · Genes & Development · doi:10.1101/gad.333205 · Cited by 229
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Background
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Adler, V., Schaffer, A., Kim, J., Dolan, L., & Ronai, Z. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.44.26071 · Cited by 223
Molecular determinants that mediate selective activation of p38 MAP kinase isoforms
Enslen, H., Brancho, D. M., & Davis, R. J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.6.1301 · Cited by 222
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BackgroundInfluentialSelf-citation
The Level of Intracellular Glutathione Is a Key Regulator for the Induction of Stress-Activated Signal Transduction Pathways Including Jun N-Terminal Protein Kinases and p38 Kinase by Alkylating Agents
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BackgroundInfluential
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Hoetzel, A., Dolinay, T., Schmidt, R., Choi, A. M. K., & Ryter, S. W. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1762 · Cited by 219
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Influential
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Rincón, M., Whitmarsh, A. J., Yang, D. D., Weiss, L., Dérijard, B., Jayaraj, P., Davis, R. J., & Flavell, R. A. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1817 · Cited by 219
“Interestingly, although MKK4 was expressed in the brain as previously described (17, 18, 20), no significant level of MKK4 gene expression was detected in thymocytes (Fig.”
BackgroundSelf-citation
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Ivaska, J., Reunanen, H., Westermarck, J. K., Koivisto, L., Kähäri, V., & Heino, J. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.2.401 · Cited by 217
“MAPKKKs shown to be effective in the p38 pathway involve ASK and TAK1 (transforming growth factor–activated kinase) (Derijard et al., 1995; Yamaguchi et al., 1995; W. Wang et al., 1997) but little is known about their upstream effectors.”
PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits
Ping, P., Zhang, J., Cao, X., Li, R. C. X., Kong, D., Tang, X., Qiu, Y., Manchikalapudi, S., Auchampach, J. A., Black, R. G., et al. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.276.5.h1468 · Cited by 218
IAP Suppression of Apoptosis Involves Distinct Mechanisms: the TAK1/JNK1 Signaling Cascade and Caspase Inhibition
Sanna, M. G., Correia, J. D. S., Ducrey, O., Lee, J., Nomoto, K., Schrantz, N., Deveraux, Q. L., & Ulevitch, R. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.6.1754-1766.2002 · Cited by 216
“Similar results were observed when using MKK4 (AA) (data not shown).”
BackgroundInfluentialSelf-citation
Extracellular Signal-regulated Protein Kinase/Jun Kinase Cross-talk Underlies Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation
Pedram, A., Razandi, M., & Levin, E. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.41.26722 · Cited by 216
Genistein Inhibits p38 Map Kinase Activation, Matrix Metalloproteinase Type 2, and Cell Invasion in Human Prostate Epithelial Cells
Huang, X., Chen, S., Xu, L., Liu, Y., Deb, D. K., Platanias, L. C., & Bergan, R. C. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2807 · Cited by 213
“identical to a previously described one (32).”
Apoptotic signaling in dopamine‐induced cell death: the role of oxidative stress, p38 mitogen‐activated protein kinase, cytochrome c and caspases
Junn, E., & Mouradian, M. M. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00425.x · Cited by 214
“MAP kinase kinase 3 (MKK3) and SAPK/ERK kinase 1 (SEK1) phosphorylate tyrosine and threonine residues at the sequence T*GY* resulting in p38 activation (Derijard et al. 1995; Raingeaud et al. 1995; Tibbles et al. 1996).”
Background
Isolation of MEK5 and Differential Expression of Alternatively Spliced Forms
English, J. M., Vanderbilt, C. A., Xu, S., Marcus, S., & Cobb, M. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28897 · Cited by 213
Thrombin Induces Activation of p38 MAP Kinase in Human Platelets
Kramer, R. M., Roberts, E. F., Strifler, B. A., & Johnstone, E. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27395 · Cited by 213
T Lymphocyte Activation Signals for Interleukin-2 Production Involve Activation of MKK6-p38 and MKK7-SAPK/JNK Signaling Pathways Sensitive to Cyclosporin A
Matsuda, S., Moriguchi, T., Koyasu, S., & Nishida, E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12378 · Cited by 213
Differential activation of ERK, JNK/SAPK and P3/CSBP/RK map kinase family members during the cellular response to arsenite
Liu, Y., Guyton, K. Z., Gorospe, M., Xu, Q., Lee, J. C., & Holbrook, N. J. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00176-1 · Cited by 213
Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms
Hou, D. X. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg184 · Cited by 212
Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle
Goodyear, L. J., Chang, P.-Y., Sherwood, D. J., Dufresne, S. D., & Moller, D. E. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.2.e403 · Cited by 211
Selective activation of the mitogen-activated protein kinase subgroups c-Jun NH2 terminal kinase and p38 by IL-1 and TNF in human articular chondrocytes.
Geng, Y., Valbracht, J., & Lotz, M. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119056 · Cited by 211
“Louis, MO) to which GST–c-Jun (1-223) was bound.”
Background
Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase
Pombo, C. M., Kehrl, J. H., Sánchez, I., Katz, P., Avruch, J., Zon, L. I., Woodgett, J. R., Force, T. L., & Kyriakis, J. M. (1995) · Nature · doi:10.1038/377750a0 · Cited by 210
NF-κB1/p105 Regulates Lipopolysaccharide-Stimulated MAP Kinase Signaling by Governing the Stability and Function of the Tpl2 Kinase
Waterfield, M. R., Zhang, M., Norman, L. P., & Sun, S. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00070-4 · Cited by 209
Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38 kDa (p38-P), stress-activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaM kinase II) are differentially expressed in tau deposits in neurons and glial cells in tauopathies
Ferrer, I., Blanco, R. E., Carmona, M., & Puig, B. (2001) · Journal of Neural Transmission · doi:10.1007/s007020100016 · Cited by 207
“The phosphorylation is mediated by the MAP kinase kinases (MKKs) (Raingeaud et al., 1995; Dérijard et al., 1995; Lin et al., 1995; Raingeaud et al., 1996; Whitmarsh and Davis, 1996; Enslen et al., 1998).”
A tyrosine kinase profile of prostate carcinoma.
Robinson, D. R., He, F., Pretlow, T. P., & Kung, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5958 · Cited by 207
Role of the Stress-activated/c-Jun NH2-terminal Protein Kinase Pathway in the Cellular Response to Adriamycin and Other Chemotherapeutic Drugs
Osborn, M. T., & Chambers, T. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.48.30950 · Cited by 207
CEP-1347 (KT7515), a Semisynthetic Inhibitor of the Mixed Lineage Kinase Family
Maroney, A. C., Finn, J. P., Connors, T. J., Durkin, J. T., Angeles, T. S., Gessner, G. W., Xu, Z., Meyer, S. L., Savage, M. J., Greene, L. A., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011601200 · Cited by 206
Cellular Stresses Differentially Activate c-Jun N-terminal Protein Kinases and Extracellular Signal-regulated Protein Kinases in Cultured Ventricular Myocytes
Bogoyevitch, M. A., Ketterman, A. J., & Sugden, P. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.50.29710 · Cited by 205
The Role of LRRK2 in Neurodegeneration of Parkinson Disease
Rui, Q., Ni, H., Li, D., Gao, R., & Chen, G. (2018) · Current Neuropharmacology · doi:10.2174/1570159x16666180222165418 · Cited by 196
“The c-Jun N-terminal kinases (JNKs), p38 MAPKs and the extracellular signalregulated kinases (ERKs) are three primary branches of the MAPK superfamily of serine/threonine protein kinases [49, 50].”
Background
Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro
Lawler, S. E., Fleming, Y., Goedert, M., & Cohen, P. (1998) · Current Biology · doi:10.1016/s0960-9822(98)00019-0 · Cited by 202
Activation of p38 Mitogen-Activated Protein Kinase and c-Jun NH2-Terminal Kinase by Double-Stranded RNA and Encephalomyocarditis Virus: Involvement of RNase L, Protein Kinase R, and Alternative Pathways
Iordanov, M. S., Paranjape, J. M., Zhou, A., Wong, J. W., Williams, B. R. G., MEURS, E. F., Silverman, R. H., & Magun, B. E. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.2.617-627.2000 · Cited by 201
“MKK4 has the ability to activate p38 MAPK as well (13).”
Background
A Conserved p38 Mitogen-Activated Protein Kinase Pathway Regulates Drosophila Immunity Gene Expression
Han, Z., Enslen, H., Hu, X., Meng, X.-J., Wu, I.-H., Barrett, T., Davis, R., & Ip, Y. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3527 · Cited by 207
“The activity of human p38 MAPKs is regulated by upstream kinases, which include MKK3 and MKK6 (12, 59).”
BackgroundInfluentialSelf-citation
JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extensionPreprint
Xia, Y., Wu, Z., Su, B., Murray, B. W., & Karin, M. (1998) · Genes & Development · doi:10.1101/gad.12.21.3369 · Cited by 203
“Surprisingly, although the sites phosphorylated by MEKK1 are within the catalytic domain of JNKK1 (Dérijard et al. 1995; Lin et al. 1995), these mutants, JNKK1(78–399) and JNKK1(89–399), were poorly phosphorylated by MEKK1 (Fig.”
BackgroundInfluential
c-Jun N-Terminal Protein Kinase 1 (JNK1), but Not JNK2, Is Essential for Tumor Necrosis Factor Alpha-Induced c-Jun Kinase Activation and Apoptosis
Liu, J., Minemoto, Y., & Lin, A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10844-10856.2004 · Cited by 201
“Two MAP2Ks (JNKK1/MKK4/SEK1 and JNKK2/MKK7) for JNK have been identified (5, 17, 18, 21).”
Background
p38 Mitogen-Activated Protein Kinase Functionally Contributes to Chondrogenesis Induced by Growth/Differentiation Factor-5 in ATDC5 Cells
Nakamura, K., Shirai, T., Morishita, S., Uchida, S., Saeki-Miura, K., & Makishima, F. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4535 · Cited by 200
Reconstitution of Mitogen-activated Protein Kinase Phosphorylation Cascades in Bacteria
Khokhlatchev, A. V., Xu, S., English, J. M., Wu, P., SCHAEFER, E. M., & Cobb, M. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.17.11057 · Cited by 200
Stress-Activated Protein Kinases in Cardiovascular Disease
Force, T. L., Pombo, C. M., Avruch, J., Bonventre, J. V., & Kyriakis, J. M. (1996) · Circulation Research · doi:10.1161/01.res.78.6.947 · Cited by 200
Selective Activation of p38 MAPK Cascade and Mitotic Arrest Caused by Low Level Oxidative Stress
Kurata, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000308200 · Cited by 199
Coupling of Jun amino-terminal kinase and Decapentaplegic signaling pathways in Drosophila morphogenesis.Preprint
Glise, B., & Noselli, S. (1997) · Genes & Development · doi:10.1101/gad.11.13.1738 · Cited by 199
Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway
Kobuchi, H., Roy, S., Sen, C. K., Nguyen, H. G., & Packer, L. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.3.c403 · Cited by 197
“A specific inhibitory effect of quercetin on JNK activity suggests that the flavonol regulated JNK activity through either direct interaction with the kinase or downregulation of upstream kinases, such as MKK4/SEK1 and MKK7, which are known to activate JNK directly by catalyzing phosphorylation (17, 49, 58).”
Background
A Proline-Rich Sequence Unique to MEK1 and MEK2 Is Required for Raf Binding and Regulates MEK Function
Catling, A. D., Schaeffer, H. J., Reuter, C. W., Reddy, G. R., & Weber, M. J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5214 · Cited by 197
“However, the mammalian MEKs differ from the yeast homologs in that they contain a proline-rich (PR) sequence between conserved kinase subdomains IX and X (11, 73, 74); this sequence is also absent from SEK1/MKK4 (18, 63).”
BackgroundInfluential
Differential Regulation of Mitogen-Activated Protein Kinases ERK1/2 and ERK5 by Neurotrophins, Neuronal Activity, and cAMP in Neurons
Cavanaugh, J. E., Ham, J., Hetman, M., Poser, S., Yan, C., & Xia, Z. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00434.2001 · Cited by 196
“Cell lysates were prepared as described previously (Dérijard et al., 1995; Xia et al., 1995), and protein concentrations were assayed by the Bradford method.”
Method
p38 Mitogen-activated Protein Kinase Negatively Regulates the Induction of Phase II Drug-metabolizing Enzymes That Detoxify Carcinogens
Yu, R., Mandlekar, S., Lei, W., Fahl, W. E., Tan, T., & Kong, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.4.2322 · Cited by 196
Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade
Buchsbaum, R. J., Connolly, B. A., & Feig, L. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.12.4073-4085.2002 · Cited by 198
“ACKNOWLEDGMENTS We thank John Collard and Marc Symons for Tiam1 clones, Roger Davis for human JIP1 and JIP2 clones, Richard Cerione for a Dbl clone, Gary Johnson for MKK3 , MKK6 , and MKK7 clones, Kathy Gallo for the MLK3 clone, Tom Roberts for the p38 and Jnk clones, and Mitchell Goldfarb for anti-IB2 antibody.”
BackgroundInfluential
The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells
Corre, I., Paris, F., & Huot, J. (2017) · Oncotarget · doi:10.18632/oncotarget.18264 · Cited by 195
“In vitro, MKK4 can also phosphorylate p38 [38].”
Background
Ultraviolet Radiation Triggers the Ribotoxic Stress Response in Mammalian Cells
Iordanov, M. S., Pribnow, D. G., Magun, J. L., Dinh, T.-H., Pearson, J. A., & Magun, B. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.25.15794 · Cited by 193
Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor.
Teng, D. H. ‐., Perry, W. L., Hogan, J. K., Baumgard, M. L., Bell, R. N., Berry, S., Davis, T., Frank, D., Frye, C., Hattier, T., et al. (1997) · PubMed · Cited by 193
A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress‐induced activation of the p38 and JNK pathways
Takekawa, M., Posas, F., & Saito, H. (1997) · The EMBO Journal · doi:10.1093/emboj/16.16.4973 · Cited by 193
“…to the yeast Ssk2 and Ssk22 MAPKKKs. activated by SEK1 (also known as MKK4) (Sánchez et al.,In mammalian cells (COS-7 and HeLa), MTK1 over1994; Dérijard et al., 1995; Lin et al., 1995); and p38 isexpression stimulated both the p38 and JNK MAP activated by either MKK3 or MKK6 (Dérijard et…”
Background
SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis
Ganiatsas, S., Kwee, L., Fujiwara, Y., Perkins, A. C., Ikeda, T., Labow, M., & Zon, L. I. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6881 · Cited by 193

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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