Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1993 Jan;12(1):307–314. doi: 10.1002/j.1460-2075.1993.tb05658.x

p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system.

M Hamaguchi 1, N Matsuyoshi 1, Y Ohnishi 1, B Gotoh 1, M Takeichi 1, Y Nagai 1
PMCID: PMC413207  PMID: 8381351

Abstract

Transformation of chick embryonic fibroblasts with Rous sarcoma virus strongly suppresses N-cadherin-mediated cell-cell adhesion, without inhibiting its expression. This suppression is correlated with tyrosine phosphorylation of N-cadherin and catenins, the cadherin-associated proteins, which are known to regulate cadherin function. Experiments with non-myristylation and temperature-sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation-specific.

Full text

PDF
307

Images in this article

Selected References

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

  1. Atkinson M. M., Menko A. S., Johnson R. G., Sheppard J. R., Sheridan J. D. Rapid and reversible reduction of junctional permeability in cells infected with a temperature-sensitive mutant of avian sarcoma virus. J Cell Biol. 1981 Nov;91(2 Pt 1):573–578. doi: 10.1083/jcb.91.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azarnia R., Loewenstein W. R. Polyomavirus middle T antigen downregulates junctional cell-to-cell communication. Mol Cell Biol. 1987 Feb;7(2):946–950. doi: 10.1128/mcb.7.2.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azarnia R., Reddy S., Kmiecik T. E., Shalloway D., Loewenstein W. R. The cellular src gene product regulates junctional cell-to-cell communication. Science. 1988 Jan 22;239(4838):398–401. doi: 10.1126/science.2447651. [DOI] [PubMed] [Google Scholar]
  4. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boller K., Vestweber D., Kemler R. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol. 1985 Jan;100(1):327–332. doi: 10.1083/jcb.100.1.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collett M. S., Erikson R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. doi: 10.1073/pnas.75.4.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper J. A., Hunter T. Identification and characterization of cellular targets for tyrosine protein kinases. J Biol Chem. 1983 Jan 25;258(2):1108–1115. [PubMed] [Google Scholar]
  8. Cooper J. A., Reiss N. A., Schwartz R. J., Hunter T. Three glycolytic enzymes are phosphorylated at tyrosine in cells transformed by Rous sarcoma virus. Nature. 1983 Mar 17;302(5905):218–223. doi: 10.1038/302218a0. [DOI] [PubMed] [Google Scholar]
  9. Cross F. R., Garber E. A., Pellman D., Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol. 1984 Sep;4(9):1834–1842. doi: 10.1128/mcb.4.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Egan S. E., Wright J. A., Jarolim L., Yanagihara K., Bassin R. H., Greenberg A. H. Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. Science. 1987 Oct 9;238(4824):202–205. doi: 10.1126/science.3659911. [DOI] [PubMed] [Google Scholar]
  11. Feldman R. A., Hanafusa T., Hanafusa H. Characterization of protein kinase activity associated with the transforming gene product of Fujinami sarcoma virus. Cell. 1980 Dec;22(3):757–765. doi: 10.1016/0092-8674(80)90552-8. [DOI] [PubMed] [Google Scholar]
  12. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fujimori T., Miyatani S., Takeichi M. Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos. Development. 1990 Sep;110(1):97–104. doi: 10.1242/dev.110.1.97. [DOI] [PubMed] [Google Scholar]
  14. Geiger B., Volk T., Volberg T., Bendori R. Molecular interactions in adherens-type contacts. J Cell Sci Suppl. 1987;8:251–272. doi: 10.1242/jcs.1987.supplement_8.14. [DOI] [PubMed] [Google Scholar]
  15. Hamaguchi M., Grandori C., Hanafusa H. Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies. Mol Cell Biol. 1988 Aug;8(8):3035–3042. doi: 10.1128/mcb.8.8.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hamaguchi M., Hanafusa H. Association of p60src with Triton X-100-resistant cellular structure correlates with morphological transformation. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2312–2316. doi: 10.1073/pnas.84.8.2312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hamaguchi M., Hanafusa H. Localization of major potential substrates of p60v-src kinase in the plasma membrane matrix fraction. Oncogene Res. 1989;4(1):29–37. [PubMed] [Google Scholar]
  18. Hamaguchi M., Matsuda M., Hanafusa H. A glycoprotein in the plasma membrane matrix as a major potential substrate of p60v-src. Mol Cell Biol. 1990 Feb;10(2):830–836. doi: 10.1128/mcb.10.2.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hanafusa H. Rapid transformation of cells by Rous sarcoma virus. Proc Natl Acad Sci U S A. 1969 Jun;63(2):318–325. doi: 10.1073/pnas.63.2.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hatta K., Takeichi M. Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature. 1986 Apr 3;320(6061):447–449. doi: 10.1038/320447a0. [DOI] [PubMed] [Google Scholar]
  21. Hirano S., Kimoto N., Shimoyama Y., Hirohashi S., Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. doi: 10.1016/0092-8674(92)90103-j. [DOI] [PubMed] [Google Scholar]
  22. Hirst R., Horwitz A., Buck C., Rohrschneider L. Phosphorylation of the fibronectin receptor complex in cells transformed by oncogenes that encode tyrosine kinases. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6470–6474. doi: 10.1073/pnas.83.17.6470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kamps M. P., Buss J. E., Sefton B. M. Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4625–4628. doi: 10.1073/pnas.82.14.4625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kamps M. P., Buss J. E., Sefton B. M. Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation. Cell. 1986 Apr 11;45(1):105–112. doi: 10.1016/0092-8674(86)90542-8. [DOI] [PubMed] [Google Scholar]
  26. Kawai S., Hanafusa H. The effects of reciprocal changes in temperature on the transformed state of cells infected with a rous sarcoma virus mutant. Virology. 1971 Nov;46(2):470–479. doi: 10.1016/0042-6822(71)90047-x. [DOI] [PubMed] [Google Scholar]
  27. Krueger J. G., Garber E. A., Goldberg A. R. Subcellular localization of pp60src in RSV-transformed cells. Curr Top Microbiol Immunol. 1983;107:51–124. [PubMed] [Google Scholar]
  28. Lagunowich L. A., Grunwald G. B. Tissue and age-specificity of post-translational modifications of N-cadherin during chick embryo development. Differentiation. 1991 May;47(1):19–27. doi: 10.1111/j.1432-0436.1991.tb00217.x. [DOI] [PubMed] [Google Scholar]
  29. LeBlanc D. J., Hawley R. J., Lee L. N., St Martin E. J. "Conjugal" transfer of plasmid DNA among oral streptococci. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3484–3487. doi: 10.1073/pnas.75.7.3484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Levinson A. D., Oppermann H., Levintow L., Varmus H. E., Bishop J. M. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell. 1978 Oct;15(2):561–572. doi: 10.1016/0092-8674(78)90024-7. [DOI] [PubMed] [Google Scholar]
  31. Matsuyoshi N., Hamaguchi M., Taniguchi S., Nagafuchi A., Tsukita S., Takeichi M. Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol. 1992 Aug;118(3):703–714. doi: 10.1083/jcb.118.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nagafuchi A., Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. doi: 10.1002/j.1460-2075.1988.tb03249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nagafuchi A., Takeichi M. Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. Cell Regul. 1989 Nov;1(1):37–44. doi: 10.1091/mbc.1.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nagafuchi A., Takeichi M., Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. doi: 10.1016/0092-8674(91)90392-c. [DOI] [PubMed] [Google Scholar]
  35. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ozawa M., Ringwald M., Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. doi: 10.1073/pnas.87.11.4246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Peyriéras N., Louvard D., Jacob F. Characterization of antigens recognized by monoclonal and polyclonal antibodies directed against uvomorulin. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8067–8071. doi: 10.1073/pnas.82.23.8067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sefton B. M., Hunter T., Ball E. H., Singer S. J. Vinculin: a cytoskeletal target of the transforming protein of Rous sarcoma virus. Cell. 1981 Apr;24(1):165–174. doi: 10.1016/0092-8674(81)90512-2. [DOI] [PubMed] [Google Scholar]
  39. Shimoyama Y., Hirohashi S. Cadherin intercellular adhesion molecule in hepatocellular carcinomas: loss of E-cadherin expression in an undifferentiated carcinoma. Cancer Lett. 1991 May 1;57(2):131–135. doi: 10.1016/0304-3835(91)90206-w. [DOI] [PubMed] [Google Scholar]
  40. Shimoyama Y., Hirohashi S. Expression of E- and P-cadherin in gastric carcinomas. Cancer Res. 1991 Apr 15;51(8):2185–2192. [PubMed] [Google Scholar]
  41. Shiozaki H., Tahara H., Oka H., Miyata M., Kobayashi K., Tamura S., Iihara K., Doki Y., Hirano S., Takeichi M. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed] [Google Scholar]
  42. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
  43. Takeichi M. Functional correlation between cell adhesive properties and some cell surface proteins. J Cell Biol. 1977 Nov;75(2 Pt 1):464–474. doi: 10.1083/jcb.75.2.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Uehara Y., Fukazawa H., Murakami Y., Mizuno S. Irreversible inhibition of v-src tyrosine kinase activity by herbimycin A and its abrogation by sulfhydryl compounds. Biochem Biophys Res Commun. 1989 Sep 15;163(2):803–809. doi: 10.1016/0006-291x(89)92293-6. [DOI] [PubMed] [Google Scholar]
  45. Uehara Y., Murakami Y., Mizuno S., Kawai S. Inhibition of transforming activity of tyrosine kinase oncogenes by herbimycin A. Virology. 1988 May;164(1):294–298. doi: 10.1016/0042-6822(88)90649-6. [DOI] [PubMed] [Google Scholar]
  46. Vestweber D., Kemler R. Some structural and functional aspects of the cell adhesion molecule uvomorulin. Cell Differ. 1984 Dec;15(2-4):269–273. doi: 10.1016/0045-6039(84)90084-8. [DOI] [PubMed] [Google Scholar]
  47. Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
  48. Volberg T., Geiger B., Dror R., Zick Y. Modulation of intercellular adherens-type junctions and tyrosine phosphorylation of their components in RSV-transformed cultured chick lens cells. Cell Regul. 1991 Feb;2(2):105–120. doi: 10.1091/mbc.2.2.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wang J. Y. Isolation of antibodies for phosphotyrosine by immunization with a v-abl oncogene-encoded protein. Mol Cell Biol. 1985 Dec;5(12):3640–3643. doi: 10.1128/mcb.5.12.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wheelock M. J., Knudsen K. A. N-cadherin-associated proteins in chicken muscle. Differentiation. 1991 Feb;46(1):35–42. doi: 10.1111/j.1432-0436.1991.tb00863.x. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES