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

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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				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]