Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold.
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.
Chodniewicz
David
D
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, SP231, La Jolla, CA 92037, USA.
Klemke
Richard L
RL
D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D050719:Crk-Associated Substrate Protein; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D016023:Integrins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; D016315:Proto-Oncogene Proteins c-abl