Etk/Bmx Tyrosine Kinase Activates Pak1 and Regulates Tumorigenicity of Breast Cancer Cells

Rozita Bagheri-Yarmand, Mahitosh Mandal, Amjad H. Taludker, Rui An Wang, Ratna K. Vadlamudi, Hsing Jien Kung, Rakesh Kumar

研究成果: 雜誌貢獻文章

99 引文 斯高帕斯(Scopus)

摘要

Etk/Bmx, a member of the Tec family of nonreceptor protein-tyrosine kinases, is characterized by an N-terminal pleckstrin homology domain and has been shown to be a downstream effector of phosphatidylinositol 3-kinase. P21-activated kinase 1 (Pak1), another well characterized effector of phosphatidylinositol 3-kinase, has been implicated in the progression of breast cancer cells. In this study, we characterized the role of Etk in mammary development and tumorigenesis and explored the functional interactions between Etk and Pak1. We report that Etk expression is developmentally regulated in the mammary gland. Using transient transfection, coimmunoprecipitation and glutathione S-transferase-pull down assays, we showed that Etk directly associates with Pak1 via its N-terminal pleckstrin homology domain and also phosphorylates Pak1 on tyrosine residues. The expression of wild-type Etk in a non-invasive human breast cancer MCF-7 cells significantly increased proliferation and anchorage-independent growth of epithelial cancer cells. Conversely, expression of kinase-inactive mutant Etk-KQ suppressed the proliferation, anchorage-independent growth, and tumorigenicity of human breast cancer MDA-MB435 cells. These results indicate that Pak1 is a target of Etk and that Etk controls the proliferation as well as the anchorage-independent and tumorigenic growth of mammary epithelial cancer cells.
原文英語
頁(從 - 到)29403-29409
頁數7
期刊Journal of Biological Chemistry
276
發行號31
DOIs
出版狀態已發佈 - 八月 3 2001
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry

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    Bagheri-Yarmand, R., Mandal, M., Taludker, A. H., Wang, R. A., Vadlamudi, R. K., Kung, H. J., & Kumar, R. (2001). Etk/Bmx Tyrosine Kinase Activates Pak1 and Regulates Tumorigenicity of Breast Cancer Cells. Journal of Biological Chemistry, 276(31), 29403-29409. https://doi.org/10.1074/jbc.M103129200