Proteolytic Activation of Etk/Bmx Tyrosine Kinase by Caspases

Yi Mi Wu, Chia Lin Huang, Hsing Jien Kung, Chi Ying F Huang

研究成果: 雜誌貢獻文章同行評審

28 引文 斯高帕斯(Scopus)

摘要

Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [ 35S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.
原文英語
頁(從 - 到)17672-17678
頁數7
期刊Journal of Biological Chemistry
276
發行號21
DOIs
出版狀態已發佈 - 1月 25 2001
對外發佈

ASJC Scopus subject areas

  • 生物化學

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