A-Raf associates with and regulates platelet-derived growth factor receptor signalling
A-Raf associates with and regulates platelet-derived growth factor receptor signalling
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DOI：
10.1016/j.cellsig.2004.11.006
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Anderson, DH
中科院分区：
文献类型：
--
作者：
Mahon, ES;Hawrysh, AD;Anderson, DH
Raf激酶是表皮生长因子（EGF）和血小板衍生生长因子（PDGF）介导的丝裂原活化蛋白激酶（MAPK）通路激活过程中的重要中间产物。在本报告中，我们表明A - Raf激酶与活化的EGF受体复合物以及血小板衍生生长因子受体（PDGFR）复合物相关联，且这种关联不依赖于先前的PDGF处理。A - Raf与受体酪氨酸激酶结合的能力可能为A - Raf的膜定位提供一种不依赖于Ras - GTP的机制。表达一种部分活化的A - Raf突变体导致血小板衍生生长因子受体的酪氨酸磷酸化降低，特别是在Y857（自身磷酸化位点）和Y1021（磷脂酶Cγ1（PLCγ1）结合位点），但不影响其他信号蛋白（Nck、磷脂酰肌醇3'-激酶（PI3K）、RasGAP、Grb2、SHP）的结合位点。活化的A - Raf表达也改变了PLCγ1和与p85相关的PI3K的活化。因此，A - Raf能够通过一种依赖于血小板衍生生长因子受体的机制调节PLCγ1信号传导，并且还可能通过一种不依赖于血小板衍生生长因子受体的机制调节PI3K信号传导。（c）2004爱思唯尔公司。保留所有权利。
Raf kinases are important intermediates in epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this report, we show that the A-Raf kinase is associated with activated EGF receptor complexes and with PDGF receptor (PDGFR) complexes independent of prior PDGF treatment. The ability of A-Raf to associate with receptor tyrosine kinases could provide a Ras-GTP-independent mechanism for the membrane localization of A-Raf. Expression of a partially activated A-Raf mutant resulted in decreased tyrosine phosphorylation of the PDGFR, specifically on Y857 (autophosphorylation site) and Y1021 (phospholipase C gamma 1 (PLC gamma 1) binding site), but not the binding sites for other signalling proteins (Nck, phosphatidylinositol 3'-kinase (PI3K), RasGAP, Grb2, SHP). Activated A-Raf expression also altered the activation of PLC gamma 1, and p85-associated PI3K. Thus, A-Raf can regulate PLC gamma 1 signalling via a PDGFR-dependent mechanism and may also regulate PI3K signalling via a PDGFR-independent mechanism. (c) 2004 Elsevier Inc. All rights reserved.