Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases.

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  • Author(s): Li L;Li L; Guris DL; Okura M; Imamoto A
  • Source:
    Molecular and cellular biology [Mol Cell Biol] 2003 Apr; Vol. 23 (8), pp. 2883-92.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: United States NLM ID: 8109087 Publication Model: Print Cited Medium: Print ISSN: 0270-7306 (Print) Linking ISSN: 02707306 NLM ISO Abbreviation: Mol Cell Biol Subsets: MEDLINE
    • Publication Information:
      Publication: 2023- : [Philadelphia] : Taylor & Francis
      Original Publication: [Washington, D.C.] : American Society for Microbiology, [c1981-
    • Subject Terms:
      Adaptor Proteins, Signal Transducing*; Focal Adhesions/*physiology ; Integrins/*physiology ; Nuclear Proteins/*physiology ; src-Family Kinases/*physiology; Animals ; Cell Movement/physiology ; Cells, Cultured ; Cytoskeleton/physiology ; Fibroblasts/physiology ; Humans ; In Vitro Techniques ; Mice ; Mice, Knockout ; Nuclear Proteins/chemistry ; Nuclear Proteins/deficiency ; Nuclear Proteins/genetics ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; cdc42 GTP-Binding Protein/metabolism ; rac1 GTP-Binding Protein/metabolism
    • Abstract:
      The adapter protein Crk-Like (CrkL) can associate with the Src substrate p130(Cas) (Cas). The biological role of CrkL downstream of Cas, however, has been largely obscure. Consistent with the ability of CrkL to biochemically associate with Cas, we found that Src triggers translocation of CrkL to focal adhesions (FAs) in a manner dependent on Cas. Forced localization of CRKL to FAs (FA-CRKL) by itself was sufficient to induce activation of Rac1 and Cdc42 and rescued haptotaxis defects of mouse embryonic fibroblasts (MEFs) lacking Src, Yes, and Fyn, three broadly expressed Src family members required for integrin-induced migration. Consistent with Rac1 activation, FA-CRKL induced cotranslocation of a Rac1 activator, Dock1, to focal adhesions. These results therefore indicate a role for CrkL in mediating Src signaling by activating small G proteins at focal adhesions. Furthermore, MEFs lacking CrkL show impaired integrin-induced migration despite expression of a closely related protein, Crk-II, in these cells. These results therefore provide formal evidence that CrkL plays a specific role in integrin-induced migration as a downstream mediator of Src.
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    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      0 (CRKL protein)
      0 (Integrins)
      0 (Nuclear Proteins)
      0 (Recombinant Fusion Proteins)
      EC 2.7.10.2 (src-Family Kinases)
      EC 3.6.5.2 (cdc42 GTP-Binding Protein)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • Publication Date:
      Date Created: 20030401 Date Completed: 20030502 Latest Revision: 20210526
    • Publication Date:
      20240829
    • Accession Number:
      PMC152569
    • Accession Number:
      10.1128/MCB.23.8.2883-2892.2003
    • Accession Number:
      12665586