Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation
Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation
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DOI：
10.1016/s1097-2765(00)80288-9
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发表时间：
1998-12-01
期刊：
影响因子：
16
通讯作者：
Neel, BG
中科院分区：
文献类型：
--
作者：
Gu, HH;Pratt, JC;Neel, BG
细胞因子信号传导的几个组成部分仍未确定。我们报道了一种这样的成分p97的克隆和初步鉴定，p97是一种广泛表达的支架蛋白，与果蝇DOS和哺乳动物Gab1有远亲关系。在细胞因子、生长因子或抗原受体刺激下，p97被酪氨酸磷酸化，并与几种含SH2结构域的蛋白（包括SHP2）结合。不能结合SHP2的p97突变体的表达阻断了细胞因子诱导的c-fos启动子激活，抑制了elk1介导的和stat5介导的交易激活。令人惊讶的是，这些突变体并不抑制MAPK的激活。我们的研究结果表明，p97是受体信号传导的一个重要调节因子，它控制着一条通往早期基因激活的新途径，并表明SHP2在细胞因子受体信号传导中具有多种功能。
Several components in cytokine signaling remain unidentified. We report the cloning and initial characterization of one such component, p97, a widely expressed scaffolding protein distantly related to Drosophila DOS and mammalian Gab1. Upon cytokine, growth factor, or antigen receptor stimulation, p97 becomes tyrosyl phosphorylated and associates with several SH2 domain-containing proteins, including SHP2. Expression of p97 mutants unable to bind SHP2 blocks cytokine-induced c-fos promotor activation, inhibiting Elk1-mediated and STAT5-medieted transactivation. Surprisingly, such mutants do not inhibit MAPK activation. Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling.