The FASEB Journal, Vol 9, 726-735, Copyright © 1995 by The Federation of American Societies for Experimental Biology

REVIEWS

The MAPK signaling cascade

R Seger and EG Krebs
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.

The transmission of extracellular signals into their intracellular targets is mediated by a network of interacting proteins that regulate a large number of cellular processes. Cumulative efforts from many laboratories over the past decade have allowed the elucidation of one such signaling mechanism, which involves activations of several membranal signaling molecules followed by a sequential stimulation of several cytoplasmic protein kinases collectively known as mitogen- activated protein kinase (MAPK) signaling cascade. Up to six tiers in this cascade contribute to the amplification and specificity of the transmitted signals that eventually activate several regulatory molecules in the cytoplasm and in the nucleus to initiate cellular processes such as proliferation, differentiation, and development. Moreover, because many oncogenes have been shown to encode proteins that transmit mitogenic signals upstream of this cascade, the MAPK pathway provides a simple unifying explanation for the mechanism of action of most, if not all, nonnuclear oncogenes. The pattern of MAPK cascade is not restricted to growth factor signaling and it is now known that signaling pathways initiated by phorbol esters, ionophors, heat shock, and ligands for seven transmembrane receptors use distinct MAPK cascades with little or no cross-reactivity between them. In this review we emphasize primarily the first MAPK cascade to be discovered that uses the MEK and ERK isoforms and describe their involvement in different cellular processes.

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				A. V. Cybulsky, R. J. Quigg, and D. J. Salant Experimental membranous nephropathy redux Am J Physiol Renal Physiol, October 1, 2005; 289(4): F660 - F671. [Abstract] [Full Text] [PDF]

				L. Minutoli, P. Antonuccio, C. Romeo, P. A. Nicotina, A. Bitto, S. Arena, F. Polito, D. Altavilla, N. Turiaco, A. Cutrupi, et al. Evidence for a Role of Mitogen-Activated Protein Kinase 3/Mitogen-Activated Protein Kinase in the Development of Testicular Ischemia-Reperfusion Injury Biol Reprod, October 1, 2005; 73(4): 730 - 736. [Abstract] [Full Text] [PDF]

				E.-R. Lee, Y.-J. Kang, J.-H. Kim, H. T. Lee, and S.-G. Cho Modulation of Apoptosis in HaCaT Keratinocytes via Differential Regulation of ERK Signaling Pathway by Flavonoids J. Biol. Chem., September 9, 2005; 280(36): 31498 - 31507. [Abstract] [Full Text] [PDF]

				M. J. Aleman, M. P. DeYoung, M. Tress, P. Keating, G. W. Perry, and R. Narayanan Inhibition of Single Minded 2 gene expression mediates tumor-selective apoptosis and differentiation in human colon cancer cells PNAS, September 6, 2005; 102(36): 12765 - 12770. [Abstract] [Full Text] [PDF]

				A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, and J. Guillemette Activation of the extracellular signal-regulated kinase by complement C5b-9 Am J Physiol Renal Physiol, September 1, 2005; 289(3): F593 - F603. [Abstract] [Full Text] [PDF]

				S. Kanda, Y. Miyata, Y. Mochizuki, T. Matsuyama, and H. Kanetake Angiopoietin 1 Is Mitogenic for Cultured Endothelial Cells Cancer Res., August 1, 2005; 65(15): 6820 - 6827. [Abstract] [Full Text] [PDF]

				H. K. Kang, H.-Y. Lee, M.-K. Kim, K. S. Park, Y. M. Park, J.-Y. Kwak, and Y.-S. Bae The Synthetic Peptide Trp-Lys-Tyr-Met-Val-D-Met Inhibits Human Monocyte-Derived Dendritic Cell Maturation via Formyl Peptide Receptor and Formyl Peptide Receptor-Like 2 J. Immunol., July 15, 2005; 175(2): 685 - 692. [Abstract] [Full Text] [PDF]

				G.-Y. Kim, K.-H. Kim, S.-H. Lee, M.-S. Yoon, H.-J. Lee, D.-O. Moon, C.-M. Lee, S.-C. Ahn, Y. C. Park, and Y.-M. Park Curcumin Inhibits Immunostimulatory Function of Dendritic Cells: MAPKs and Translocation of NF-{kappa}B as Potential Targets J. Immunol., June 15, 2005; 174(12): 8116 - 8124. [Abstract] [Full Text] [PDF]

				M. E. McMullen, P. W. Bryant, C. C. Glembotski, P. A. Vincent, and K. M. Pumiglia Activation of p38 Has Opposing Effects on the Proliferation and Migration of Endothelial Cells J. Biol. Chem., June 3, 2005; 280(22): 20995 - 21003. [Abstract] [Full Text] [PDF]

				C. Mawrin, T. Sasse, E. Kirches, S. Kropf, T. Schneider, C. Grimm, C. Pambor, C. K. Vorwerk, R. Firsching, U. Lendeckel, et al. Different Activation of Mitogen-Activated Protein Kinase and Akt Signaling Is Associated with Aggressive Phenotype of Human Meningiomas Clin. Cancer Res., June 1, 2005; 11(11): 4074 - 4082. [Abstract] [Full Text] [PDF]

				A. C. Bellott, K. C. Patel, and T. J. Burkholder Reduction of caveolin-3 expression does not inhibit stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes J Appl Physiol, April 1, 2005; 98(4): 1554 - 1561. [Abstract] [Full Text] [PDF]

				S. Sela-Abramovich, E. Chorev, D. Galiani, and N. Dekel Mitogen-Activated Protein Kinase Mediates Luteinizing Hormone-Induced Breakdown of Communication and Oocyte Maturation in Rat Ovarian Follicles Endocrinology, March 1, 2005; 146(3): 1236 - 1244. [Abstract] [Full Text] [PDF]

				M. Chu, J. Guo, and C.-Y. Chen Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition J. Biol. Chem., February 25, 2005; 280(8): 6369 - 6379. [Abstract] [Full Text] [PDF]

				L. Qin, J. Tamasi, L. Raggatt, X. Li, J. H. M. Feyen, D. C. Lee, E. DiCicco-Bloom, and N. C. Partridge Amphiregulin Is a Novel Growth Factor Involved in Normal Bone Development and in the Cellular Response to Parathyroid Hormone Stimulation J. Biol. Chem., February 4, 2005; 280(5): 3974 - 3981. [Abstract] [Full Text] [PDF]

				D. S. Hutchinson and T. Bengtsson {alpha}1A-Adrenoceptors Activate Glucose Uptake in L6 Muscle Cells through a Phospholipase C-, Phosphatidylinositol-3 Kinase-, and Atypical Protein Kinase C-Dependent Pathway Endocrinology, February 1, 2005; 146(2): 901 - 912. [Abstract] [Full Text] [PDF]

				M. Bustamante, U. Hasler, O. Kotova, A. V. Chibalin, D. Mordasini, M. Rousselot, A. Vandewalle, P.-Y. Martin, and E. Feraille Insulin potentiates AVP-induced AQP2 expression in cultured renal collecting duct principal cells Am J Physiol Renal Physiol, February 1, 2005; 288(2): F334 - F344. [Abstract] [Full Text] [PDF]

				H. J. Song, T. S. Lee, J. H. Jeong, Y. S. Min, C. Y. Shin, and U. D. Sohn Hydrogen Peroxide-Induced Extracellular Signal-Regulated Kinase Activation in Cultured Feline Ileal Smooth Muscle Cells J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 391 - 398. [Abstract] [Full Text] [PDF]

				L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]

				M. Rahaus, N. Desloges, and M. H. Wolff Replication of varicella-zoster virus is influenced by the levels of JNK/SAPK and p38/MAPK activation J. Gen. Virol., December 1, 2004; 85(12): 3529 - 3540. [Abstract] [Full Text] [PDF]