The integrin alpha 7 cytoplasmic domain regulates cell migration, lamellipodia formation, and p130CAS/Crk coupling

J Biol Chem. 2001 Apr 20;276(16):13417-26. doi: 10.1074/jbc.M011481200. Epub 2001 Jan 12.


The integrin alpha(7)beta(1) is the major laminin-binding integrin in skeletal, heart, and smooth muscle and is a receptor for laminin-1 and -2. It mediates myoblast migration on laminin-1 and -2 and thus might be involved in muscle development and repair. Previously we have shown that alpha(7)B as well as the alpha(7)A and -C splice variants induce cell motility on laminin when transfected into nonmotile HEK293 cells. In this study we have investigated the role of the cytoplasmic domain of alpha(7) in the laminin-induced signal transduction of alpha(7)beta(1) integrin regulating cell adhesion and migration. Deletion of the cytoplasmic domain did not affect assembly of the mutated alpha(7)Deltacyt/beta(1) heterodimer on the cell surface or adhesion of alpha(7)Deltacyt-transfected cells to laminin. The motility of these cells on the laminin-1/E8 fragment, however, was significantly reduced to the level of mock-transfected cells; lamellipodia formation and polarization of the cells were also impaired. Adhesion to the laminin-1/E8 fragment induced tyrosine phosphorylation of the focal adhesion kinase, paxillin, and p130(CAS) as well as the formation of a p130(CAS)-Crk complex in wild-type alpha(7)B-transfected cells. In alpha(7)BDeltacyt cells, however, the extent of p130(CAS) tyrosine formation was reduced and formation of the p130(CAS)-Crk complex was impaired, with unaltered levels of p130(CAS) and Crk protein levels. These findings indicate adhesion-dependent regulation of p130(CAS)/Crk complex formation by the cytoplasmic domain of alpha(7)B integrin after cell adhesion to laminin-1/E8 and imply alpha(7)B-controlled lamellipodia formation and cell migration through the p130(CAS)/Crk protein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / chemistry*
  • Antigens, CD / physiology*
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Membrane / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cell Polarity
  • Cytoplasm / physiology
  • Dimerization
  • Humans
  • Integrin alpha Chains*
  • Laminin / pharmacology
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-cbl
  • Pseudopodia / physiology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Signal Transduction
  • Transfection
  • Ubiquitin-Protein Ligases*


  • Antigens, CD
  • Integrin alpha Chains
  • Laminin
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • integrin alpha7
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • CBL protein, human