UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3
UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3
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DOI：
10.1016/j.cellsig.2006.06.003
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Vojtek, Anne B.
中科院分区：
文献类型：
--
作者：
Avery, Adam W.;Figueroa, Claudia;Vojtek, Anne B.
β-51-like kinases（ULK）是进化上保守的丝氨酸/苏氨酸特异性蛋白激酶亚家族的成员。在这里，我们报告成纤维细胞生长因子受体底物（FRS）2/3是新的ULK 2羧基端结构域相互作用蛋白。FRS 2/3是作为衔接蛋白介导多种受体酪氨酸激酶信号传导的同源物。ULK 2与FRS 2/3的磷酸酪氨酸结合（PTB）结构域相互作用。我们证明，在小鼠P19细胞中靶向ULK 2的siRNA导致FGFR 1介导的FRS 3和SHP 2酪氨酰磷酸化升高。此外，RNAi介导的ULK 2减少导致FGFR 1和FRS 3之间的相互作用增加。ULK 2在体外磷酸化FRS 2/3，表明ULK 2介导的磷酸化可能是FRS 2/3调节的机制。所呈现的数据支持ULK 2通过与FRS 2/3相互作用和抑制SynGAP而负调节FGFR 1下游信号蛋白的酪氨酰磷酸化的模型。(c)2006年爱思唯尔公司All rights reserved.
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.