Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein

Elena Kurenova, Li Hui Xu, Xihui Yang, Albert S. Baldwin, Rolf J. Craven, Steven K. Hanks, Zheng Gang Liu, William G. Cance

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine kinase that is overexpressed in a variety of human tumors, mediates one of these survival signals. Attenuation of FAK expression in tumor cells results in apoptosis that is mediated by caspase 8-and FADD-dependent pathways, suggesting that death receptor pathways are involved in the process. Here, we report a functional link between FAK and death receptors. We have demonstrated that FAK binds to the death domain kinase receptor-interacting protein (RIP). RIP is a major component of the death receptor complex and has been shown to interact with Fas and tumor necrosis factor receptor 1 through its binding to adapter proteins. We have shown that RIP provides proapoptotic signals that are suppressed by its binding to FAK. We thus propose that FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex.

Original languageEnglish
Pages (from-to)4361-4371
Number of pages11
JournalMolecular and Cellular Biology
Volume24
Issue number10
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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