Functional regulation of Brk through its substrate p190RhoGAP
Date Issued
2007
Date
2007
Author(s)
Lin, Ming-Shien
DOI
en-US
Abstract
Breast tumor kinase (Brk) is a nonreceptor tyrosine kinase that belongs to Src-like kinase family that 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 caner types. However, the molecular mechanism of that Brk participates in tumorigenesis remains to be characterized. Brk overexpression has been shown to sensitize mammary epithelial cells to epidermal growth factor (EGF). In this study, we have generated antibody against Brk which specifically recognizes both exogenous and endogenous Brk. Moreover, this Brk specific antibody can be utilized for immunoprecipitation to pull down both exogenous and endogenous Brk. In addition, we have characterized p190RhoGAP as a novel substrate of Brk and further identified the major phosphorylation site Y1105. Furthermore, we have discovered the involvement of Brk in EGF-induced p190RhoGAP phosphorylation on Y1105. This phosphorylation promotes the membrane recruitment of p190RhoGAP in response to EGF stimulation. In addition, the result that knockdown of Brk can inhibit the cell spreading implies the biological effect of Brk in cell motility. Finally, we have demonstrated that Brk is capable of promoting cell proliferation through a p190RhoGAP-dependent manner. Together, our findings identify new signaling and biological roles of Brk and indicate the potential link between Brk and both cell motility and proliferation which may contribute to its involvement in tumorigenesis.
Subjects
乳癌激酶
Brk
p190RhoGAP
SDGs
Type
other
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