Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells

Johannes Grossmann, Monika Artinger, Adam W. Grasso, Hsing Jien Kung, Jürgen Schölmerich, Claudio Fiocchi, Alan D. Levine

研究成果: 雜誌貢獻文章同行評審

51 引文 斯高帕斯(Scopus)

摘要

Background & Aims: Purified intestinal epithelial cells die of detachment-induced apoptosis due to loss of cell anchorage during isolation. Anchorage-dependent cells form focal adhesions, sites of enhanced cell-matrix attachment that confer survival signals. Focal adhesion kinase (FAK), a component of the focal adhesion signaling complex, transduces these antiapoptotic signals. In this report, the molecular events leading to cleavage of FAK by caspases during apoptosis and its functional implications are defined. Methods: Cytosolic extracts of human intestinal epithelial cells undergoing detachment-induced apoptosis were analyzed by Western blotting, immunoprecipitation, and kinase assay. Results: FAK is cleaved by the ordered proteolytic activity of 2 different members of the caspase-3 family. The first cleavage is mediated by caspase-3, generating a 94/92-kilodalton-terminal fragment, which is processed by caspase-6 to an 84-kilodalton fragment. After apoptosis is initiated, the level of FAK phosphorylation is rapidly decreased, and the phosphorylation pattern of FAK-associated proteins is dramatically modified, showing significant yet divergent changes in signal transduction. Conclusions: Cleavage of FAK during apoptosis of normal human cells is an example of the sequential, highly regulated, and coordinate action of caspases that not only dismantle a cell by proteolysis, but also alter the cell's signaling machinery.
原文英語
頁(從 - 到)79-88
頁數10
期刊Gastroenterology
120
發行號1
DOIs
出版狀態已發佈 - 一月 1 2001
對外發佈Yes

ASJC Scopus subject areas

  • Gastroenterology

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