The Lipid Raft-Anchored Adaptor Protein Cbp Controls the Oncogenic Potential of c-Src
- 作者：Chitose Oneyama ; Tomoya Hikita ; Kengo Enya ; Marc-Werner Dobenecker ; Kazunobu Saito ; Shigeyuki Nada ; Alex ; er Tarakhovsky ; Masato Okada
- 关键词：SIGNALING ; CELLCYCLE
- 刊名：Molecular Cell
- 出版年：2008
- 期刊代码：111_10972765
- 类别：bio
- 出版时间：23 May 2008
- 卷：30
- 期：4
- 页码：426-436
- 文件大小：1659 K
摘要
The tyrosine kinase c-Src is upregulated in various human cancers irrespective of its negative regulator Csk, but the regulatory mechanisms remain unclear. Here, we show that a lipid raft-anchored Csk adaptor, Cbp/PAG, is directly involved in controlling the oncogenicity of c-Src. Using Csk-deficient cells that can be transformed by c-Src overexpression, we found that Cbp expression is markedly downregulated by c-Src activation and re-expression of Cbp efficiently suppresses c-Src transformation as well as tumorigenesis. Cbp-deficient cells are more susceptible to v-Src transformation than their parental cells. Upon phosphorylation, Cbp specifically binds to activated c-Src and sequesters it in lipid rafts, resulting in an efficient suppression of c-Src function independent of Csk. In some human cancer cells and tumors, Cbp is downregulated and the introduction of Cbp significantly suppresses tumorigenesis. These findings indicate a potential role for Cbp as a suppressor of c-Src-mediated tumor progression.