|Title:||Brk Activates Rac1 and Promotes Cell Migration and Invasion by Phosphorylating Paxillin||Authors:||CHEN, HSIN-YI
|Issue Date:||2004||Journal Volume:||v.24||Journal Issue:||n.24||Start page/Pages:||10558-10572||Source:||MOLECULAR AND CELLULAR BIOLOGY||Abstract:||
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.
|Appears in Collections:||分子醫學研究所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.