TY - JOUR
T1 - Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein
AU - Kurenova, Elena
AU - Xu, Li Hui
AU - Yang, Xihui
AU - Baldwin, Albert S.
AU - Craven, Rolf J.
AU - Hanks, Steven K.
AU - Liu, Zheng Gang
AU - Cance, William G.
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.24.10.4361-4371.2004
DO - 10.1128/MCB.24.10.4361-4371.2004
M3 - Article
C2 - 15121855
AN - SCOPUS:2942531163
SN - 0270-7306
VL - 24
SP - 4361
EP - 4371
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 10
ER -