期刊
MOLECULAR ONCOLOGY
卷 3, 期 5-6, 页码 439-450出版社
WILEY
DOI: 10.1016/j.molonc.2009.07.001
关键词
Kinase; Mass spectrometry; Phosphoproteomics; Phosphorylation; Signal transduction; SILAC; c-Src; PDGF
类别
资金
- National Institutes of Health [CA106424, U54 RR020839]
- National Heart, Lung, and Blood Institute, National Institutes of Health [HV-28180]
- Department of Defense Era of Hope Scholar award [W81XWH-06-1-0428]
- Department of Defense Breast Cancer Research Program [W81XVvH-05-1-0304]
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. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据