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Endocrine Reviews 22 (2): 153-183
Copyright © 2001 by The Endocrine Society

Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions1

Gray Pearson, Fred Robinson, Tara Beers Gibson, Bing-e Xu, Mahesh Karandikar, Kevin Berman and Melanie H. Cobb

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.




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H.-L. Chang, Y.-C. Wu, J.-H. Su, Y.-T. Yeh, and S.-S. F. Yuan
Protoapigenone, a Novel Flavonoid, Induces Apoptosis in Human Prostate Cancer Cells through Activation of p38 Mitogen-Activated Protein Kinase and c-Jun NH2-Terminal Kinase 1/2
J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 841 - 849.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
J. Sun, R. D. Ramnath, L. Zhi, R. Tamizhselvi, and M. Bhatia
Substance P enhances NF-{kappa}B transactivation and chemokine response in murine macrophages via ERK1/2 and p38 MAPK signaling pathways
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1586 - C1596.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. Almog, S. Lazar, N. Reiss, N. Etkovitz, E. Milch, N. Rahamim, M. Dobkin-Bekman, R. Rotem, M. Kalina, J. Ramon, et al.
Identification of Extracellular Signal-regulated Kinase 1/2 and p38 MAPK as Regulators of Human Sperm Motility and Acrosome Reaction and as Predictors of Poor Spermatozoan Quality
J. Biol. Chem., May 23, 2008; 283(21): 14479 - 14489.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. L. Callejas-Valera, J. Guinea-Viniegra, C. Ramirez-Castillejo, J. A. Recio, E. Galan-Moya, N. Martinez, J. M. Rojas, S. R. y Cajal, and R. Sanchez-Prieto
E1a Gene Expression Blocks the ERK1/2 Signaling Pathway by Promoting Nuclear Localization and MKP Up-regulation: IMPLICATION IN v-H-Ras-INDUCED SENESCENCE
J. Biol. Chem., May 9, 2008; 283(19): 13450 - 13458.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
C. Chen, R. E. Lewis, and M. A. White
IMP Modulates KSR1-dependent Multivalent Complex Formation to Specify ERK1/2 Pathway Activation and Response Thresholds
J. Biol. Chem., May 9, 2008; 283(19): 12789 - 12796.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
H.-M. Zhang, L. Li, N. Papadopoulou, G. Hodgson, E. Evans, M. Galbraith, M. Dear, S. Vougier, J. Saxton, and P. E. Shaw
Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1
Nucleic Acids Res., May 1, 2008; 36(8): 2594 - 2607.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. Sethu, G. Mendez-Corao, and A. J. Melendez
Phospholipase D1 Plays a Key Role in TNF-{alpha} Signaling
J. Immunol., May 1, 2008; 180(9): 6027 - 6034.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Y.-H. Yang, Y. Wang, K. S.L. Lam, M.-H. Yau, K. K.Y. Cheng, J. Zhang, W. Zhu, D. Wu, and A. Xu
Suppression of the Raf/MEK/ERK Signaling Cascade and Inhibition of Angiogenesis by the Carboxyl Terminus of Angiopoietin-Like Protein 4
Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 835 - 840.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
C. Ma, K. A. Bower, G. Chen, X. Shi, Z.-J. Ke, and J. Luo
Interaction between ERK and GSK3{beta} Mediates Basic Fibroblast Growth Factor-induced Apoptosis in SK-N-MC Neuroblastoma Cells
J. Biol. Chem., April 4, 2008; 283(14): 9248 - 9256.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
T. Lotan, J. Hickson, J. Souris, D. Huo, J. Taylor, T. Li, K. Otto, S. D. Yamada, K. Macleod, and C. W. Rinker-Schaeffer
c-Jun NH2-Terminal Kinase Activating Kinase 1/Mitogen-Activated Protein Kinase Kinase 4-Mediated Inhibition of SKOV3ip.1 Ovarian Cancer Metastasis Involves Growth Arrest and p21 Up-regulation
Cancer Res., April 1, 2008; 68(7): 2166 - 2175.
[Abstract] [Full Text] [PDF]


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J. Leukoc. Biol.Home page
G. Adhikary, Y. Sun, and E. Pearlman
C-Jun NH2 terminal kinase (JNK) is an essential mediator of Toll-like receptor 2-induced corneal inflammation
J. Leukoc. Biol., April 1, 2008; 83(4): 991 - 997.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
S. L. Fougner, J. Bollerslev, F. Latif, J. K. Hald, T. Lund, J. Ramm-Pettersen, and J. P. Berg
Low Levels of Raf Kinase Inhibitory Protein in Growth Hormone-Secreting Pituitary Adenomas Correlate with Poor Response to Octreotide Treatment
J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1211 - 1216.
[Abstract] [Full Text] [PDF]


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FASEB J.Home page
M. R. Junttila, S.-P. Li, and J. Westermarck
Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival
FASEB J, April 1, 2008; 22(4): 954 - 965.
[Abstract] [Full Text] [PDF]


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Toxicol SciHome page
S. Wang, M. Tang, B. Pei, X. Xiao, J. Wang, H. Hang, and L. Wu
Cadmium-Induced Germline Apoptosis in Caenorhabditis elegans: The Roles of HUS1, p53, and MAPK Signaling Pathways
Toxicol. Sci., April 1, 2008; 102(2): 345 - 351.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
A. Gadea, S. Schinelli, and V. Gallo
Endothelin-1 Regulates Astrocyte Proliferation and Reactive Gliosis via a JNK/c-Jun Signaling Pathway
J. Neurosci., March 5, 2008; 28(10): 2394 - 2408.
[Abstract] [Full Text] [PDF]


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Integr Cancer TherHome page
C. Guruvayoorappan and G. Kuttan
Biophytum sensitivum (L.) DC Inhibits Tumor Cell Invasion and Metastasis Through a Mechanism Involving Regulation of MMPs, Prolyl Hydroxylase, Lysyl Oxidase, nm23, ERK-1, ERK-2, STAT-1, and Proinflammatory Cytokine Gene Expression in Metastatic Lung Tissue
Integr Cancer Ther, March 1, 2008; 7(1): 42 - 50.
[Abstract] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
C. Li, B. Ge, M. Nicotra, J. N. H. Stern, H. D. Kopcow, X. Chen, and J. L. Strominger
JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity
PNAS, February 26, 2008; 105(8): 3017 - 3022.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
S.-H. Lee, H.-S. Choi, H. Kim, and Y. Lee
ERK is a novel regulatory kinase for poly(A) polymerase
Nucleic Acids Res., February 11, 2008; 36(3): 803 - 813.
[Abstract] [Full Text] [PDF]


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Hum Mol GenetHome page
G. Esposito, J. Imitola, J. Lu, D. De Filippis, C. Scuderi, V. S. Ganesh, R. Folkerth, J. Hecht, S. Shin, T. Iuvone, et al.
Genomic and functional profiling of human Down syndrome neural progenitors implicates S100B and aquaporin 4 in cell injury
Hum. Mol. Genet., February 1, 2008; 17(3): 440 - 457.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
J. Xie and M. S. Roberson
3', 5'-Cyclic Adenosine 5'-Monophosphate Response Element-Dependent Transcriptional Regulation of the Secretogranin II Gene Promoter Depends on Gonadotropin-Releasing Hormone-Induced Mitogen-Activated Protein Kinase Activation and the Transactivator Activating Transcription Factor 3
Endocrinology, February 1, 2008; 149(2): 783 - 792.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. Yogi, C. Mercure, J. Touyz, G. E. Callera, A. C.I. Montezano, A. B. Aranha, R. C. Tostes, T. Reudelhuber, and R. M. Touyz
Renal Redox-Sensitive Signaling, but Not Blood Pressure, Is Attenuated by Nox1 Knockout in Angiotensin II-Dependent Chronic Hypertension
Hypertension, February 1, 2008; 51(2): 500 - 506.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Wang, M. Zhu, M. Ayalew, and J. A. Ruff
Down-regulation of Pkc1-mediated Signaling by the Deubiquitinating Enzyme Ubp3
J. Biol. Chem., January 25, 2008; 283(4): 1954 - 1961.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M.-H. Lee, H. M. El-Shewy, D. K. Luttrell, and L. M. Luttrell
Role of -Arrestin-mediated Desensitization and Signaling in the Control of Angiotensin AT1a Receptor-stimulated Transcription
J. Biol. Chem., January 25, 2008; 283(4): 2088 - 2097.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
L. Li, E. Abdel Fattah, G. Cao, C. Ren, G. Yang, A. A. Goltsov, A. C. Chinault, W.-W. Cai, T. L. Timme, and T. C. Thompson
Glioma Pathogenesis-Related Protein 1 Exerts Tumor Suppressor Activities through Proapoptotic Reactive Oxygen Species c-Jun NH2 Kinase Signaling
Cancer Res., January 15, 2008; 68(2): 434 - 443.
[Abstract] [Full Text] [PDF]


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IOVSHome page
J.-A. Ko, Y. Liu, R. Yanai, T.-i. Chikama, T. Takezawa, and T. Nishida
Upregulation of Tight-Junctional Proteins in Corneal Epithelial Cells by Corneal Fibroblasts in Collagen Vitrigel Cultures
Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 113 - 119.
[Abstract] [Full Text] [PDF]


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J. Leukoc. Biol.Home page
D. J. Weiss, C. D. Souza, O. A. Evanson, M. Sanders, and M. Rutherford
Bovine monocyte TLR2 receptors differentially regulate the intracellular fate of Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium
J. Leukoc. Biol., January 1, 2008; 83(1): 48 - 55.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
C. G. Ziegler, F. Sicard, P. Lattke, S. R. Bornstein, M. Ehrhart-Bornstein, and A. W. Krug
Dehydroepiandrosterone Induces a Neuroendocrine Phenotype in Nerve Growth Factor-Stimulated Chromaffin Pheochromocytoma PC12 Cells
Endocrinology, January 1, 2008; 149(1): 320 - 328.
[Abstract] [Full Text] [PDF]


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JCBHome page
G. W. Pearson and T. Hunter
Real-time imaging reveals that noninvasive mammary epithelial acini can contain motile cells
J. Cell Biol., December 31, 2007; 179(7): 1555 - 1567.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
J. Wang, J.-Y. Zhou, and G. S. Wu
ERK-Dependent MKP-1 Mediated Cisplatin Resistance in Human Ovarian Cancer Cells
Cancer Res., December 15, 2007; 67(24): 11933 - 11941.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
H. Vaidyanathan, J. Opoku-Ansah, S. Pastorino, H. Renganathan, M. L. Matter, and J. W. Ramos
ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15
PNAS, December 11, 2007; 104(50): 19837 - 19842.
[Abstract] [Full Text] [PDF]


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J Mol EndocrinolHome page
M. Nakamura, B. Han, T. Nishishita, Y. Bai, and K. Kakudo
Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers
J. Mol. Endocrinol., December 1, 2007; 39(6): 375 - 384.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
M.-Y. Han, H. Kosako, T. Watanabe, and S. Hattori
Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Regulates Actin Organization and Cell Motility by Phosphorylating the Actin Cross-Linking Protein EPLIN
Mol. Cell. Biol., December 1, 2007; 27(23): 8190 - 8204.
[Abstract] [Full Text] [PDF]




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