The docking protein FRS2α controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors

被引：124

作者：

Lax, I ^{[1
]}

Wong, A ^{[1
]}

Lamothe, B ^{[1
]}

Lee, A ^{[1
]}

Frost, A ^{[1
]}

Hawes, J ^{[1
]}

Schlessinger, J ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA

来源：

MOLECULAR CELL | 2002年 / 10卷 / 04期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1016/S1097-2765(02)00689-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The docking protein FRS2alpha functions as a major mediator of signaling by FGF and NGF receptors. Here we demonstrate that, in addition to tyrosine phosphorylation, FRS2alpha is phosphorylated by MAP kinase on multiple threonine residues in response to FGF stimulation or by insulin, EGF, and PDGF, extracellular stimuli that do not induce tyrosine phosphorylation of FRS2alpha. Prevention of FRS2alpha threonine phosphorylation results in constitutive tyrosine phosphorylation of FRS2a in unstimulated cells and enhanced tyrosine phosphorylation of FRS2alpha, MAPK stimulation, cell migration, and proliferation in FGF-stimulated cells. Expression of an FRS2alpha mutant deficient in MAPK phosphorylation sites induces anchorage-independent cell growth and colony formation in soft agar. These experiments reveal a novel MAPK-mediated, negative feedback mechanism for control of signaling pathways that are dependent on FRS2 and a mechanism for heterologous control of signaling via FGF receptors.

引用

页码：709 / 719

页数：11

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