Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2

Biochem J. 2003 Mar 15;370(Pt 3):1039-45. doi: 10.1042/BJ20021308.

Abstract

Tensin1 is an actin- and phosphotyrosine-binding protein that localizes to focal adhesions. Recently, we have shown that both tensin1 and a new family member, tensin2, promote cell migration [Chen, Duncan, Bozorgchami and Lo (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 733-738]. Since localization of proteins to particular intracellular compartments often regulates their functions, and Src homology domain 2 may mediate signals related to cell migration, we hypothesize that tensin-mediated cell migration is regulated by the focal adhesion localization and the Src homology domain 2 of tensin. To test this hypothesis, we have analysed the effects of a series of tensin1 mutants on cell migration. Our results have shown that (1) tensin1 contains two focal adhesion-binding sites, (2) the wild-type tensin1 significantly promotes cell migration, (3) mutants with one focal adhesion-binding site do not promote cell migration, (4) the non-focal adhesion localized mutant suppresses cell migration and (5) the mutant that is not able to bind to phosphotyrosine-containing proteins has no effect on cell migration. These results have indicated that focal adhesion localization of tensin1 and the phosphotyrosine-binding activity are two critical factors in regulating tensin-mediated cell migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Movement / physiology*
  • Chickens
  • Cytoskeletal Proteins / metabolism
  • Focal Adhesions / metabolism*
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Paxillin
  • Peptide Fragments / metabolism
  • Phosphoproteins / metabolism
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Tensins
  • src Homology Domains*

Substances

  • Actins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Paxillin
  • Peptide Fragments
  • Phosphoproteins
  • Pxn protein, mouse
  • Recombinant Fusion Proteins
  • Tensins
  • Tns1 protein, mouse