Identification of c-Src tyrosine kinase substrates in platelet-derived growth factor receptor signaling.
Identification of c-Src tyrosine kinase substrates in platelet-derived growth factor receptor signaling.
复制标题
DOI：
10.1016/j.molonc.2009.07.001
复制
发表时间：
2009-12
影响因子：
6.6
通讯作者：
Pandey A
中科院分区：
文献类型：
--
作者：
Amanchy R;Zhong J;Hong R;Kim JH;Gucek M;Cole RN;Molina H;Pandey A
c-Src非受体酪氨酸激酶是血小板衍生生长因子（PDGF）受体信号通路的重要组成部分。c-Src已被证明可介导成纤维细胞对PDGF的有丝分裂反应。然而，c-Src介导的PDGF受体信号通路的确切成分尚不清楚。在这里，我们使用细胞培养氨基酸的稳定同位素标记（SILAC）结合质谱法鉴定了参与PDGF信号传导的Src家族激酶底物。使用SILAC，我们能够检测PDGF受体信号传导中43种潜在c-Src激酶底物酪氨酸磷酸化模式的变化。这包括23种已知的c-Src激酶底物，其中16种蛋白已知在PDGF信号传导中起作用，而其余7种蛋白先前未涉及PDGF受体信号传导。重要的是，我们的分析还鉴定了20个新的Src家族激酶底物，其中5个蛋白先前被报道为PDGF受体信号通路的中间体，其余15个蛋白代表PDGF受体信号通路的新型信号中间体。在验证实验中，我们证明PDGF确实以c-Src依赖的方式诱导候选Src家族激酶底物（calpain2、Eps15和Trim28）的一个子集的磷酸化。
c-Src non-receptor tyrosine kinase is an important component of the platelet-derived growth factor (PDGF) receptor signaling pathway. c-Src has been shown to mediate the mitogenic response to PDGF in fibroblasts. However, the exact components of PDGF receptor signaling pathway mediated by c-Src remain unclear. Here, we used stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to identify Src family kinase substrates involved in PDGF signaling. Using SILAC, we were able to detect changes in tyrosine phosphorylation patterns of 43 potential c-Src kinase substrates in PDGF receptor signaling. This included 23 known c-Src kinase substrates, of which 16 proteins have known roles in PDGF signaling while the remaining 7 proteins have not previously been implicated in PDGF receptor signaling. Importantly, our analysis also led to identification of 20 novel Src family kinase substrates, of which 5 proteins were previously reported as PDGF receptor signaling pathway intermediates while the remaining 15 proteins represent novel signaling intermediates in PDGF receptor signaling. In validation experiments, we demonstrated that PDGF indeed induced the phosphorylation of a subset of candidate Src family kinase substrates – Calpain 2, Eps15 and Trim28 – in a c-Src-dependent fashion.
登录
查看更多内容
影响因子：
5.3
作者：
CARPENTER, CL;AUGER, KR;CANTLEY, LC
通讯作者：
CANTLEY, LC
影响因子：
46.9
作者：
Blagoev, B;Ong, SE;Mann, M
通讯作者：
Mann, M
影响因子：
64.8
作者：
BAGRODIA, S;CHACKALAPARAMPIL, I;SHALLOWAY, D
通讯作者：
SHALLOWAY, D
影响因子：
4.8
作者：
Fraser, RA;Heard, DJ;Chambon, P
通讯作者：
Chambon, P
影响因子：
4.8
作者：
Furge, LL;Chen, K;Cohen, S
通讯作者：
Cohen, S