Roles of the MAP Kinase Cascade in Vertebrates

doi:10.1016/S1054-3589(08)60579-7

Advances in Pharmacology

Volume 36, 1996, Pages 121-137

https://doi.org/10.1016/S1054-3589(08)60579-7 Get rights and content

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This chapter focuses on the roles of the MAP kinase cascade in mammalian cultured cells and Xenopus systems. One of the most outstanding characteristics of MAP kinases is their activation mechanism. Activation of MAP kinases requires the phos- phorylation of both threonine and tyrosine residues in the sequence “TEY” located between kinase subdomains VII and VIII. MAP kinase is commonly activated by a large number of extracellular stimuli and is supposed to play a key role in various intracellular signal transduction pathways because MAP kinase can phosphorylate many target substrates in vitro. However, few have been shown to be substrates for MAP kinase in vivo. In PC12 cells, both NGF and epidermal growth factor (EGF) activate 43-kDa MAP kinase (ERK1) and 41-kDa MAP kinase (ERK2). The EGF-induced activation of MAP kinases is transient, whereas the NGF-induced activation is sustained and is accompanied by nuclear translocation of MAP kinases. Fully grown Xelzopus oocytes are naturally arrested at prophase of meiosis I. Progesterone releases this arrest and induces progression through meiosis. The activities of MAPKK and MAP kinase are elevated at about the same time as MPF during progesterone-induced oocyte maturation, suggesting the possibility of a positive feedback loop between the MAP kinase cascade and MPF. The MAP kinase cascade is activated by various extracellular stimuli. Evidence is accumulating suggesting the involvement of the MAP kinase cascade in a wide variety of cellular responses including differentiation of PC12 cells, proliferation of fibroblasts, Xenopus oocyte maturation, metaphase arrest, and mesoderm induction as summarized in the chapter.

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Roles of the MAP Kinase Cascade in Vertebrates

Publisher Summary

J. Biol. Chem.

Curr. Biol.

Cell

Trends Biochem. Sci.

Trends Biochern. Sci.

Cell

Cell

Cell

Trends Biochem. Sci.

J. Biol. Chem.

Trends Biochem. Sci.

Cell

Curr. Opin. Genet. Dev.

Cell

Cell

Cell

J. Biol. Chem.

J. Biol. Chem.

Dev. Biol.

J. Biol. Chem.

Cell

J. Biol. Chem.

Cell

Biochim. Biopbys. Acta

J. Biol. Cbem.

Cell

J. Biol Cbem.

J. Biol. Gem.

J. Biol. Cbem.

Curr. Opin. Cell Biol.

J. Biol. Chem.

J. Biol. Cbem.

Cell

J. Biol. Chem.

Neuron

J. Biol. Chem.

FEBS Lett.

Trends Biochem. Sci.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell

Selective requirement for MAP kinase activation in thyrnocyte differentiation

Nature

Identification of the sites in MAP kinase kinase-l phosphorylated by p74raf-1

EMBO J.

Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase

Nature

The amino acid sequence of a mammalian MAP kinase kinase

Oncogene

Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation

Cell

An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control

Science

Constitutive MAP kinase phosphatase (MPK-1) expression blocks G1 specific gene transcription and S-phase entry in fibroblasts

Oncogene

MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues

Cell Growth Differ.

Identification of the sites in MAP kinase kinase-l phosphorylated by p74^raf-1