The ERK Cascade: a Prototype of MAPK Signaling

Overview

Journal Mol Biotechnol

Publisher Springer

Specialties Biotechnology
Molecular Biology

Date 2005 Sep 20

PMID 16170216

Citations 174

Authors

Hadara Rubinfeld

Rony Seger

Affiliations

Soon will be listed here.

Abstract

Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. Four such cascades have been elucidated thus far, and named according to their MAPK tier component as the ERK1/2, JNK, p38MAPK, and ERK5 cascades. These cascades cooperate in transmitting various extracellular signals, and thus control cellular processes such as proliferation, differentiation, development, stress response, and apoptosis. Here we describe the classic ERK1/2 cascade, and concentrate mainly on the properties of MEK1/2 and ERK1/2, including their mode of regulation and their role in various cellular processes and in oncogenesis. This cascade may serve as a prototype of the other MAPK cascades, and the study of this cascade is likely to contribute to the understanding of mitogenic and other processes in many cell lines and tissues.

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References

Johnson G, Lapadat R . Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002; 298(5600):1911-2. DOI: 10.1126/science.1072682. View

Abe M, Kahle K, Saelzler M, Orth K, Dixon J, Rosner M . ERK7 is an autoactivated member of the MAPK family. J Biol Chem. 2001; 276(24):21272-9. DOI: 10.1074/jbc.M100026200. View

Han J, Lee J, Bibbs L, Ulevitch R . A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994; 265(5173):808-11. DOI: 10.1126/science.7914033. View

Holland P, Suzanne M, Campbell J, Noselli S, Cooper J . MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous. J Biol Chem. 1997; 272(40):24994-8. DOI: 10.1074/jbc.272.40.24994. View

Ray L, Sturgill T . Rapid stimulation by insulin of a serine/threonine kinase in 3T3-L1 adipocytes that phosphorylates microtubule-associated protein 2 in vitro. Proc Natl Acad Sci U S A. 1987; 84(6):1502-6. PMC: 304462. DOI: 10.1073/pnas.84.6.1502. View

Northwood I, Gonzalez F, Wartmann M, Raden D, Davis R . Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669. J Biol Chem. 1991; 266(23):15266-76. View

Morton S, Davis R, Mclaren A, Cohen P . A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. EMBO J. 2003; 22(15):3876-86. PMC: 169061. DOI: 10.1093/emboj/cdg388. View

Sewing A, Wiseman B, Lloyd A, Land H . High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1. Mol Cell Biol. 1997; 17(9):5588-97. PMC: 232407. DOI: 10.1128/MCB.17.9.5588. View

Seger R, Ahn N, Posada J, Munar E, Jensen A, Cooper J . Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. J Biol Chem. 1992; 267(20):14373-81. View

10.

Marshall C . Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995; 80(2):179-85. DOI: 10.1016/0092-8674(95)90401-8. View

11.

Zheng C, Guan K . Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J. 1994; 13(5):1123-31. PMC: 394921. DOI: 10.1002/j.1460-2075.1994.tb06361.x. View

12.

Derijard B, Hibi M, Wu I, Barrett T, Su B, Deng T . JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994; 76(6):1025-37. DOI: 10.1016/0092-8674(94)90380-8. View

13.

Serrano M, Lin A, McCurrach M, Beach D, Lowe S . Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997; 88(5):593-602. DOI: 10.1016/s0092-8674(00)81902-9. View

14.

Bogoyevitch M, Court N . Counting on mitogen-activated protein kinases--ERKs 3, 4, 5, 6, 7 and 8. Cell Signal. 2004; 16(12):1345-54. DOI: 10.1016/j.cellsig.2004.05.004. View

15.

Leevers S, PATERSON H, Marshall C . Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature. 1994; 369(6479):411-4. DOI: 10.1038/369411a0. View

16.

Hibi M, Lin A, Smeal T, Minden A, Karin M . Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993; 7(11):2135-48. DOI: 10.1101/gad.7.11.2135. View

17.

Roux P, Blenis J . ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004; 68(2):320-44. PMC: 419926. DOI: 10.1128/MMBR.68.2.320-344.2004. View

18.

Marmor M, Skaria K, Yarden Y . Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 2004; 58(3):903-13. DOI: 10.1016/j.ijrobp.2003.06.002. View

19.

Moore T, Garg R, JOHNSON C, Coptcoat M, Ridley A, Morris J . PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization. J Biol Chem. 2000; 275(6):4311-22. DOI: 10.1074/jbc.275.6.4311. View

20.

Dorow D, Devereux L, Tu G, Price G, Nicholl J, Sutherland G . Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2. Eur J Biochem. 1995; 234(2):492-500. DOI: 10.1111/j.1432-1033.1995.492_b.x. View