https://scholars.lib.ntu.edu.tw/handle/123456789/337533
Title: | Breast tumor kinase phosphorylates p190RhoGAP to regulate Rho and ras and promote breast carcinoma growth, migration, and invasion | Authors: | Shen, Che-Hung Chen, Hsin-Yi Lin, Ming-Shien Li, Fang-Yen Chang, Cheng-Chi Kuo, Min-Liang Settleman, Jeffrey Chen, Ruey-Hwa SHEN, CHE-HUNG CHEN, HSIN-YI LIN, MING- SHIEN LI, FANG-YEN CHANG, CHENG-CHI KUO, MIN-LIANG CHEN, RUEY-HWA |
Issue Date: | 2008 | Journal Volume: | 68 | Journal Issue: | 19 | Start page/Pages: | 7779-7787 | Source: | Cancer Research | Abstract: | Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is overexpressed in breast cancer and several other cancer types. Our previous study indicates that Brk promotes cell migration and tumor invasion by phosphorylating the focal adhesion protein paxillin. Here, we report the identification of p190RhoGAP-A (p190) as a Brk substrate. Brk phosphorylates p190 at the Y1105 residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120). As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively. In carcinoma cells expressing high levels of Brk, endogenous Brk functions as a key contributor to epidermal growth factor-induced p190 tyrosine phosphorylation. We present evidence showing that p190 phosphorylation plays essential roles in both migratory and proliferative effects of Brk. Furthermore, disruption of p190 phosphorylation-induced p190/p120 complex in breast cancer cells abolishes not only the abilities of Brk to regulate RhoA and Ras but also the stimulatory effects of Brk on proliferation, migration, invasion, transformation, and tumorigenicity. Together, our findings reveal a previously unknown function of Brk in regulating both RhoA and Ras by phosphorylating p190 and provide evidence for the crucial roles of this Brk-elicited signaling pathway in promoting breast malignancy. ?2008 American Association for Cancer Research. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-54249162412&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/337533 |
DOI: | 10.1158/0008-5472.CAN-08-0997 | SDG/Keyword: | protein p190; Ras protein; Rho factor; RhoA guanine nucleotide binding protein; animal cell; article; breast carcinoma; breast tumor; carcinogenicity; cell invasion; cell migration; controlled study; embryo; human; human cell; in vitro study; mouse; nonhuman; priority journal; protein expression; protein phosphorylation |
Appears in Collections: | 生化科學研究所 |
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