GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor
GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor
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DOI：
10.1128/mcb.24.2.875-885.2004
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发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Berk, BC
中科院分区：
文献类型：
--
作者：
Yin, GY;Haendeler, J;Berk, BC
以细胞外信号调节激酶（ERK 1/2）为代表的丝裂原活化蛋白激酶途径的活化和上游激酶（MEK 1）的活化是生长因子信号转导的关键事件。c-Sre已被提议作为响应G蛋白偶联受体（GPCR）和酪氨酸激酶偶联受体（TKR）的这些信号的常见介体。在这里，我们表明，GPCR激酶相互作用蛋白1（GIT 1）是一个基板的c-Src，与MEK 1在血管平滑肌细胞和人胚肾293细胞。61 T1通过卷曲螺旋结构域和Spa 2同源结构域的结合是在用血管紧张素II和表皮生长因子刺激后持续激活MEK 1-ERK 1/2所必需的。我们认为GIT 1作为一种支架蛋白，促进c-Src依赖性MEK 1-ERKI/2激活，以响应GPCR和TKR。
Activation of the mitogen-activated protein kinase pathway represented by extracellular signal-regulated kinases (ERK1/2) and activation of the upstream kinase (MEK1) are critical events for growth factor signal transduction. c-Sre has been proposed as a common mediator for these signals in response to both G protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs). Here we show that the GPCR kinase-interacting protein 1 (GIT1) is a substrate for c-Src that associates with MEK1 in vascular smooth-muscle cells and human embryonic kidney 293 cells. 61T1 binding via coiled-coil domains and a Spa2 homology domain is required for sustained activation of MEK1-ERK1/2 after stimulation with angiotensin II and epidermal growth factor. We propose that GIT1 serves as a scaffold protein to facilitate c-Src-dependent activation of MEK1-ERKI/2 in response to both GPCRs and TKRs.