UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3

被引：13

作者：

Avery, Adam W. ^{[1
]}

Figueroa, Claudia ^{[1
]}

Vojtek, Anne B. ^{[1
]}

机构：

[1] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

来源：

CELLULAR SIGNALLING | 2007年 / 19卷 / 01期

关键词：

UNC-51-like kinase; ULK2; FRS2; FRS3; FRS2alpha; FRS2beta; FGFR; PTB domain;

D O I：

10.1016/j.cellsig.2006.06.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

UNC-51-like kinases (ULK) are members of an evolutionarily conserved sub-family of ubiquitously expressed serine/threonine-specific protein kinases. Here we report that fibroblast growth factor receptor substrate (FRS) 2/3 are novel ULK2 carboxy-terminal domain interacting proteins. FRS2/3 are homologs that function as adaptor proteins to mediate signaling of multiple receptor tyrosine kinases. ULK2 interacts with the phospho-tyrosine binding (PTB) domain of FRS2/3. We demonstrate that siRNA targeting ULK2 in mouse P19 cells results in elevated FGFR1 mediated FRS3 and SHP2 tyrosyl phosphorylation. In addition, RNAi-mediated decrease in ULK2 causes increased interaction between FGFR1 and FRS3. ULK2 phosphorylates FRS2/3 in vitro, suggesting that ULK2 mediated phosphorylation may be a mechanism of FRS2/3 regulation. The data presented support a model in which ULK2, by interaction with FRS2/3 and inhibition of SynGAP, functions to negatively regulate tyrosyl phosphorylation of signaling proteins downstream of FGFR1. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：177 / 184

页数：8

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