Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2003 Mar 15;370(Pt 3):1039–1045. doi: 10.1042/BJ20021308

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

Huaiyang Chen 1, Su Hao Lo 1
PMCID: PMC1223245  PMID: 12495434

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.

Full Text

The Full Text of this article is available as a PDF (288.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bansal A., Gierasch L. M. The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation. Cell. 1991 Dec 20;67(6):1195–1201. doi: 10.1016/0092-8674(91)90295-a. [DOI] [PubMed] [Google Scholar]
  2. Bear J. E., Loureiro J. J., Libova I., Fässler R., Wehland J., Gertler F. B. Negative regulation of fibroblast motility by Ena/VASP proteins. Cell. 2000 Jun 23;101(7):717–728. doi: 10.1016/s0092-8674(00)80884-3. [DOI] [PubMed] [Google Scholar]
  3. Bendori R., Salomon D., Geiger B. Identification of two distinct functional domains on vinculin involved in its association with focal contacts. J Cell Biol. 1989 Jun;108(6):2383–2393. doi: 10.1083/jcb.108.6.2383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birchmeier C., Birchmeier W., Brand-Saberi B. Epithelial-mesenchymal transitions in cancer progression. Acta Anat (Basel) 1996;156(3):217–226. doi: 10.1159/000147848. [DOI] [PubMed] [Google Scholar]
  5. Bockholt S. M., Burridge K. Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem. 1993 Jul 15;268(20):14565–14567. [PubMed] [Google Scholar]
  6. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  7. Calderwood David A., Yan Boxu, de Pereda Jose M., Alvarez Begoña García, Fujioka Yosuke, Liddington Robert C., Ginsberg Mark H. The phosphotyrosine binding-like domain of talin activates integrins. J Biol Chem. 2002 Apr 3;277(24):21749–21758. doi: 10.1074/jbc.M111996200. [DOI] [PubMed] [Google Scholar]
  8. Cary L. A., Han D. C., Polte T. R., Hanks S. K., Guan J. L. Identification of p130Cas as a mediator of focal adhesion kinase-promoted cell migration. J Cell Biol. 1998 Jan 12;140(1):211–221. doi: 10.1083/jcb.140.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen Huaiyang, Duncan Ian C., Bozorgchami Hormozd, Lo Su Hao. Tensin1 and a previously undocumented family member, tensin2, positively regulate cell migration. Proc Natl Acad Sci U S A. 2002 Jan 15;99(2):733–738. doi: 10.1073/pnas.022518699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clark E. A., Brugge J. S. Integrins and signal transduction pathways: the road taken. Science. 1995 Apr 14;268(5208):233–239. doi: 10.1126/science.7716514. [DOI] [PubMed] [Google Scholar]
  11. Davis S., Lu M. L., Lo S. H., Lin S., Butler J. A., Druker B. J., Roberts T. M., An Q., Chen L. B. Presence of an SH2 domain in the actin-binding protein tensin. Science. 1991 May 3;252(5006):712–715. doi: 10.1126/science.1708917. [DOI] [PubMed] [Google Scholar]
  12. Giancotti F. G., Ruoslahti E. Integrin signaling. Science. 1999 Aug 13;285(5430):1028–1032. doi: 10.1126/science.285.5430.1028. [DOI] [PubMed] [Google Scholar]
  13. Greener T., Zhao X., Nojima H., Eisenberg E., Greene L. E. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. J Biol Chem. 2000 Jan 14;275(2):1365–1370. doi: 10.1074/jbc.275.2.1365. [DOI] [PubMed] [Google Scholar]
  14. Gumbiner B. M. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996 Feb 9;84(3):345–357. doi: 10.1016/s0092-8674(00)81279-9. [DOI] [PubMed] [Google Scholar]
  15. Hayashi M., Suzuki H., Kawashima S., Saido T. C., Inomata M. The behavior of calpain-generated N- and C-terminal fragments of talin in integrin-mediated signaling pathways. Arch Biochem Biophys. 1999 Nov 15;371(2):133–141. doi: 10.1006/abbi.1999.1427. [DOI] [PubMed] [Google Scholar]
  16. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  17. Ishii A., Lo S. H. A role of tensin in skeletal-muscle regeneration. Biochem J. 2001 Jun 15;356(Pt 3):737–745. doi: 10.1042/0264-6021:3560737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jiang B., Yamamura S., Nelson P. R., Mureebe L., Kent K. C. Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways. Surgery. 1996 Aug;120(2):427–432. doi: 10.1016/s0039-6060(96)80319-9. [DOI] [PubMed] [Google Scholar]
  19. Jockusch B. M., Bubeck P., Giehl K., Kroemker M., Moschner J., Rothkegel M., Rüdiger M., Schlüter K., Stanke G., Winkler J. The molecular architecture of focal adhesions. Annu Rev Cell Dev Biol. 1995;11:379–416. doi: 10.1146/annurev.cb.11.110195.002115. [DOI] [PubMed] [Google Scholar]
  20. Kim T. H., Bowen W. C., Stolz D. B., Runge D., Mars W. M., Michalopoulos G. K. Differential expression and distribution of focal adhesion and cell adhesion molecules in rat hepatocyte differentiation. Exp Cell Res. 1998 Oct 10;244(1):93–104. doi: 10.1006/excr.1998.4209. [DOI] [PubMed] [Google Scholar]
  21. Kioka N., Sakata S., Kawauchi T., Amachi T., Akiyama S. K., Okazaki K., Yaen C., Yamada K. M., Aota S. Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. J Cell Biol. 1999 Jan 11;144(1):59–69. doi: 10.1083/jcb.144.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klemke R. L., Leng J., Molander R., Brooks P. C., Vuori K., Cheresh D. A. CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J Cell Biol. 1998 Feb 23;140(4):961–972. doi: 10.1083/jcb.140.4.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lehto V. P., Virtanen I. Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230). J Cell Biol. 1983 Mar;96(3):703–716. doi: 10.1083/jcb.96.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lo S. H., An Q., Bao S., Wong W. K., Liu Y., Janmey P. A., Hartwig J. H., Chen L. B. Molecular cloning of chick cardiac muscle tensin. Full-length cDNA sequence, expression, and characterization. J Biol Chem. 1994 Sep 2;269(35):22310–22319. [PubMed] [Google Scholar]
  25. Lo S. H., Yu Q. C., Degenstein L., Chen L. B., Fuchs E. Progressive kidney degeneration in mice lacking tensin. J Cell Biol. 1997 Mar 24;136(6):1349–1361. doi: 10.1083/jcb.136.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nuckolls G. H., Turner C. E., Burridge K. Functional studies of the domains of talin. J Cell Biol. 1990 May;110(5):1635–1644. doi: 10.1083/jcb.110.5.1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rodríguez Fernández J. L., Geiger B., Salomon D., Ben-Ze'ev A. Overexpression of vinculin suppresses cell motility in BALB/c 3T3 cells. Cell Motil Cytoskeleton. 1992;22(2):127–134. doi: 10.1002/cm.970220206. [DOI] [PubMed] [Google Scholar]
  28. Rosenfeld G. C., Hou D. C., Dingus J., Meza I., Bryan J. Isolation and partial characterization of human platelet vinculin. J Cell Biol. 1985 Mar;100(3):669–676. doi: 10.1083/jcb.100.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Salgia R., Brunkhorst B., Pisick E., Li J. L., Lo S. H., Chen L. B., Griffin J. D. Increased tyrosine phosphorylation of focal adhesion proteins in myeloid cell lines expressing p210BCR/ABL. Oncogene. 1995 Sep 21;11(6):1149–1155. [PubMed] [Google Scholar]
  30. Schoenwaelder S. M., Burridge K. Bidirectional signaling between the cytoskeleton and integrins. Curr Opin Cell Biol. 1999 Apr;11(2):274–286. doi: 10.1016/s0955-0674(99)80037-4. [DOI] [PubMed] [Google Scholar]
  31. Schwartz M. A., Schaller M. D., Ginsberg M. H. Integrins: emerging paradigms of signal transduction. Annu Rev Cell Dev Biol. 1995;11:549–599. doi: 10.1146/annurev.cb.11.110195.003001. [DOI] [PubMed] [Google Scholar]
  32. Vignoud L., Usson Y., Balzac F., Tarone G., Block M. R. Internalization of the alpha 5 beta 1 integrin does not depend on "NPXY" signals. Biochem Biophys Res Commun. 1994 Mar 15;199(2):603–611. doi: 10.1006/bbrc.1994.1271. [DOI] [PubMed] [Google Scholar]
  33. Zambrano N., Buxbaum J. D., Minopoli G., Fiore F., De Candia P., De Renzis S., Faraonio R., Sabo S., Cheetham J., Sudol M. Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins. J Biol Chem. 1997 Mar 7;272(10):6399–6405. doi: 10.1074/jbc.272.10.6399. [DOI] [PubMed] [Google Scholar]
  34. Zhou M. M., Ravichandran K. S., Olejniczak E. F., Petros A. M., Meadows R. P., Sattler M., Harlan J. E., Wade W. S., Burakoff S. J., Fesik S. W. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature. 1995 Dec 7;378(6557):584–592. doi: 10.1038/378584a0. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES