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

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10558-10572
Number of pages15
JournalMolecular and Cellular Biology
Volume24
Issue number24
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Fingerprint

Paxillin
Cell Movement
Phosphotransferases
Breast Neoplasms
Epidermal Growth Factor
Protein-Tyrosine Kinases
Phosphorylation
Monomeric GTP-Binding Proteins
Catalytic Domain
Neoplasms
Carcinogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin. / Chen, Hsin Yi; Shen, Che Hung; Tsai, Yuh Tyng; Lin, Feng Chi; Huang, Yuan Ping; Chen, Ruey Hwa.

In: Molecular and Cellular Biology, Vol. 24, No. 24, 12.2004, p. 10558-10572.

Research output: Contribution to journalArticle

Chen, Hsin Yi ; Shen, Che Hung ; Tsai, Yuh Tyng ; Lin, Feng Chi ; Huang, Yuan Ping ; Chen, Ruey Hwa. / Brk activates Rac1 and promotes cell migration and invasion by phosphorylating paxillin. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 24. pp. 10558-10572.
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