Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2.
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.
Chen
Huaiyang
H
Department of Orthopaedic Surgery, Center for Tissue Regeneration and Repair, University of California, Davis, Sacramento, CA 95817, USA.
Lo
Su Hao
SH
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051419:Paxillin; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000070876:Tensins; D018909:src Homology Domains
D000199:Actins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D051419:Paxillin; D010446:Peptide Fragments; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D011993:Recombinant Fusion Proteins; D000070876:Tensins; C000603373:Tns1 protein, mouse