scholarly journals Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein

2004 ◽  
Vol 24 (10) ◽  
pp. 4361-4371 ◽  
Author(s):  
Elena Kurenova ◽  
Li-Hui Xu ◽  
Xihui Yang ◽  
Albert S. Baldwin ◽  
Rolf J. Craven ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Death Receptor ◽  
Human Tumors ◽  
Receptor Complex ◽  
Death Domain ◽  
Functional Link ◽  
Interacting Protein ◽  
Survival Signals

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.

scholarly journals Receptor-interacting Protein Shuttles between Cell Death and Survival Signaling Pathways

2010 ◽  
Vol 21 (3) ◽  
pp. 481-488 ◽  
Author(s):  
Pachiyappan Kamarajan ◽  
Julius Bunek ◽  
Yong Lin ◽  
Gabriel Nunez ◽  
Yvonne L. Kapila
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Focal Adhesion Kinase ◽  
Signaling Pathways ◽  
Focal Adhesion ◽  
Death Domain ◽  
Reverse Effect ◽  
Interacting Protein ◽  
Survival Pathways ◽  
Survival Signaling

Cross-talk between apoptosis and survival signaling pathways is crucial for regulating tissue processes and mitigating disease. We report that anoikis—apoptosis triggered by loss of extracellular matrix contacts—activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated survival pathways. RIP's death domain was critical for RIP and Fas association to mediate anoikis. Fas or RIP attenuation reduced this association and suppressed anoikis, whereas their overexpression had the reverse effect. Overexpressing FAK restored RIP and FAK association and inhibited anoikis. Thus, RIP shuttles between CD95/Fas death and FAK survival signaling to mediate anoikis.

Early signalling events of autophagy

2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Interacting Protein ◽  
The Core ◽  
Autophagy Gene ◽  
Autophagy Induction ◽  
Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

scholarly journals Dynamics of RASSF1A/MOAP-1 Association with Death Receptors

2008 ◽  
Vol 28 (14) ◽  
pp. 4520-4535 ◽  
Author(s):  
Caitlin J. Foley ◽  
Holly Freedman ◽  
Sheryl L. Choo ◽  
Christina Onyskiw ◽  
Nai Yang Fu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor Receptor ◽  
Death Receptor ◽  
Death Receptors ◽  
Tumor Formation ◽  
Receptor Interaction ◽  
Binding Motif ◽  
Death Domain ◽  
Interacting Protein ◽  
Receptor Complexes ◽  
Tnf Α

ABSTRACT RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis utilizing the Bax-interacting protein MOAP-1 (previously referred to as MAP-1). However, the dynamics of death receptor recruitment of RASSF1A and MOAP-1 are still not understood. We have now detailed recruitment to death receptors (tumor necrosis factor receptor 1 [TNF-R1] and TRAIL-R1/DR4) and identified domains of RASSF1A and MOAP-1 that are required for death receptor interaction. Upon TNF-α stimulation, the C-terminal region of MOAP-1 associated with the death domain of TNF-R1; subsequently, RASSF1A was recruited to MOAP-1/TNF-R1 complexes. Prior to recruitment to TNF-R1/MOAP-1 complexes, RASSF1A homodimerization was lost. RASSF1A associated with the TNF-R1/MOAP-1 or TRAIL-R1/MOAP-1 complex via its N-terminal cysteine-rich (C1) domain containing a potential zinc finger binding motif. Importantly, TNF-R1 association domains on both MOAP-1 and RASSF1A were essential for death receptor-dependent apoptosis. The association of RASSF1A and MOAP-1 with death receptors involves an ordered recruitment to receptor complexes to promote cell death and inhibit tumor formation.

Focal Adhesion Kinase and Protein Kinase B Cooperate to Suppress Doxorubicin-Induced Apoptosis of Breast Tumor Cells

2006 ◽  
Vol 70 (4) ◽  
pp. 1330-1339 ◽  
Author(s):  
Maroesja J. van Nimwegen ◽  
Merei Huigsloot ◽  
Annamarie Camier ◽  
Ine B. Tijdens ◽  
Bob van de Water
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Breast Tumor ◽  
Protein Kinase B ◽  
Breast Tumor Cells ◽  
Induced Apoptosis

scholarly journals Resistance of Tumor Cells to Cytolytic T Lymphocytes Involves Rho-GTPases and Focal Adhesion Kinase Activation

2008 ◽  
Vol 283 (46) ◽  
pp. 31665-31672 ◽  
Author(s):  
Soraya Abouzahr-Rifai ◽  
Meriem Hasmim ◽  
Habib Boukerche ◽  
Jocelyne Hamelin ◽  
Bassam Janji ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Rho Gtpases ◽  
Cytolytic T Lymphocytes ◽  
Kinase Activation

scholarly journals Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression

2012 ◽  
Vol 197 (7) ◽  
pp. 907-919 ◽  
Author(s):  
Ssang-Taek Lim ◽  
Nichol L.G. Miller ◽  
Xiao Lei Chen ◽  
Isabelle Tancioni ◽  
Colin T. Walsh ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Nuclear Localization ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
C Terminus ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Α

Vascular cell adhesion molecule–1 (VCAM-1) plays important roles in development and inflammation. Tumor necrosis factor–α (TNF-α) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin–matrix signaling, respectively. Integrin costimulatory signals modulate inflammatory gene expression, but the important control points between these pathways remain unresolved. We report that pharmacological FAK inhibition prevented TNF-α–induced VCAM-1 expression within heart vessel–associated endothelial cells in vivo, and genetic or pharmacological FAK inhibition blocked VCAM-1 expression during development. FAK signaling facilitated TNF-α–induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-α–induced VCAM-1 production. FAK inhibition also triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase–dependent polyubiquitination and degradation. These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover.

Neuregulin Induces the Rapid Association of Focal Adhesion Kinase with the erbB2–erbB3 Receptor Complex in Schwann Cells

2000 ◽  
Vol 271 (2) ◽  
pp. 414-417 ◽  
Author(s):  
Timothy Vartanian ◽  
Andrew Goodearl ◽  
Sharon Lefebvre ◽  
Song-Kyu Park ◽  
Gerald Fischbach
Keyword(s):  
Focal Adhesion Kinase ◽  
Schwann Cells ◽  
Focal Adhesion ◽  
Receptor Complex
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