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

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.

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Laminin–sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts

The Journal of Cell Biology ◽

10.1083/jcb.200501098 ◽

2005 ◽

Vol 169 (1) ◽

pp. 179-189 ◽

Cited By ~ 97

Author(s):

Shaohua Li ◽

Patricia Liquari ◽

Karen K. McKee ◽

David Harrison ◽

Raj Patel ◽

...

Keyword(s):

Basement Membrane ◽

Schwann Cell ◽

Focal Adhesion Kinase ◽

Schwann Cells ◽

Focal Adhesion ◽

Receptor Signaling ◽

Cell Surfaces ◽

Β1 Integrins ◽

Focal Adhesion Kinase Phosphorylation ◽

Kinase Phosphorylation

Endoneurial laminins (Lms), β1-integrins, and dystroglycan (DG) are important for Schwann cell (SC) ensheathment and myelination of axons. We now show that SC expression of galactosyl-sulfatide, a Lm-binding glycolipid, precedes that of Lms in developing nerves. This glycolipid anchors Lm-1 and -2 to SC surfaces by binding to their LG domains and enables basement membrane (BM) assembly. Revealingly, non–BM-forming fibroblasts become competent for BM assembly when sulfatides are intercalated into their cell surfaces. Assembly is characterized by coalescence of sulfatide, DG, and c-Src into a Lm-associated complex; by DG-dependent recruitment of utrophin and Src activation; and by integrin-dependent focal adhesion kinase phosphorylation. Collectively, our findings suggest that sulfated glycolipids are key Lm anchors that determine which cell surfaces can assemble Lms to initiate BM assembly and DG- and integrin-mediated signaling.

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Association of β1 Integrin with Focal Adhesion Kinase and Paxillin in Differentiating Schwann Cells

Journal of Neuroscience ◽

10.1523/jneurosci.20-10-03776.2000 ◽

2000 ◽

Vol 20 (10) ◽

pp. 3776-3784 ◽

Cited By ~ 76

Author(s):

Li-Mei Chen ◽

Debora Bailey ◽

Cristina Fernandez-Valle

Keyword(s):

Focal Adhesion Kinase ◽

Schwann Cells ◽

Focal Adhesion ◽

Β1 Integrin

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Early signalling events of autophagy

Essays in Biochemistry ◽

10.1042/bse0550001 ◽

2013 ◽

Vol 55 ◽

pp. 1-15 ◽

Cited By ~ 16

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.

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