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Published on: March 8, 2017
Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold
David Chodniewicz1, Richard L Klemke
1Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, SP231, La Jolla, CA 92037, USA.
Abstract:
The molecular coupling of CAS and Crk in response to integrin activation is an evolutionary conserved signaling module that controls cell proliferation, survival and migration. However, when deregulated, CAS/Crk signaling also contributes to cancer progression and developmental defects in humans. Here we highlight recent advances in our understanding of how CAS/Crk complexes assemble in cells to modulate the actin cytoskeleton, and the molecular mechanisms that regulate this process. We discuss in detail the spatiotemporal dynamics of CAS/Crk assembly and how this scaffold recruits specific effector proteins that couple integrin signaling networks to the migration machinery of cells. We also highlight the importance of CAS/Crk signaling in the dual regulation of cell migration and survival mechanisms that operate in invasive cells during development and pathological conditions associated with cancer metastasis.
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