Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin

Hsin Yi Chen, Che Hung Shen, Yuh Tyng Tsai, Feng Chi Lin, Yuan Ping Huang, Ruey Hwa Chen

研究成果: 雜誌貢獻文章同行評審

127 引文 斯高帕斯(Scopus)

摘要

Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy.
原文英語
頁(從 - 到)10558-10572
頁數15
期刊Molecular and Cellular Biology
24
發行號24
DOIs
出版狀態已發佈 - 十二月 2004
對外發佈Yes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

指紋 深入研究「Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin」主題。共同形成了獨特的指紋。

引用此