Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation
文献类型:期刊论文
作者 | Jiang, LQ; Feng, X; Zhou, W; Knyazev, PG; Ullrich, A; Chen, Z |
刊名 | ONCOGENE
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出版日期 | 2006 |
卷号 | 25期号:40页码:5495-5506 |
关键词 | Cbp EGFR cell transformation Src Csk |
通讯作者 | Chen, Z (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Proteom, Room 210,Bldg 23,320 Yue Yang Rd, Shanghai 200031, Peoples R China.,zjchen@sibs.ac.cn |
英文摘要 | Epidermal growth factor receptor (EGFR) and Src tyrosine kinase cooperate in regulating EGFR-mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions. Activation of Src is tightly regulated by the C-terminal Src kinase (Csk). The Csk-binding protein (Cbp) is a ubiquitously expressed transmembrane protein. Its functions include suppression of T-cell receptor activation through recruiting Csk and inhibiting Src family kinase (SFK). However, a potential role of Cbp in EGF-induced cell activities has not been investigated. Here, we report that EGF-stimulation-induced Cbp tyrosine phosphorylation followed by Cbp-Csk association, in a SFK-dependent manner. Expression of wild-type (wt) Cbp remarkably suppressed EGF-induced activation of Src, ERK1/2, and Akt-1 enzymes, and NIH3T3 cell transformation, as well as colony formation of a breast cancer cell line (MDAMB468) in soft agar. In contrast, expression of CbpY317F or knockdown endogenous Cbp in NIH3T3 cells by RNA interference significantly enhanced EGF-induced activation of these enzymes and cell transformation. In addition, overexpression of multiple receptor tyrosine kinases (RTKs)-induced Cbp tyrosine phosphorylation. These results demonstrate that Cbp functions as a negative regulator of cell transformation and tumor cell growth through downregulation of Src activation, suggesting that Cbp might be broadly involved in RTKs-activated signaling pathways and tumorigenesis. |
学科主题 | Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
类目[WOS] | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
关键词[WOS] | GLYCOSPHINGOLIPID-ENRICHED MICRODOMAINS ; FAMILY TYROSINE KINASES ; C-SRC ; FACTOR RECEPTOR ; TRANSMEMBRANE ADAPTER ; AKT ACTIVATION ; BREAST-CANCER ; DNA-SYNTHESIS ; LIPID RAFTS ; PHOSPHORYLATION |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000240370400003 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1808] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Jiang, LQ,Feng, X,Zhou, W,et al. Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation[J]. ONCOGENE,2006,25(40):5495-5506. |
APA | Jiang, LQ,Feng, X,Zhou, W,Knyazev, PG,Ullrich, A,&Chen, Z.(2006).Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation.ONCOGENE,25(40),5495-5506. |
MLA | Jiang, LQ,et al."Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation".ONCOGENE 25.40(2006):5495-5506. |
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