title: Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold.
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.
authors.affiliation: Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, SP231, La Jolla, CA 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chodniewicz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Klemke
mesh_terms: 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
chemical_list: 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