Logo of biochemjBJ Latest papers and much more!
Biochem J. Jul 1, 1996; 317(Pt 1): 279–284.
PMCID: PMC1217474

Intestinal HT-29 cells with dysfunction of E-cadherin show increased pp60src activity and tyrosine phosphorylation of p120-catenin.

Abstract

1. HT-29 M6 cells are a subpopulation of HT-29 cells that, contrarily to the parental cells, establish tight cell contacts and differentiate. Cell-to-cell contacts in HT-29 M6 cells are also regulated by protein kinase C; addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) decreases the homotypic contacts of these cells. We show here that HT-29 cells or HT-29 M6 cells treated with PMA contain lower levels of functional E-cadherin, determined by analysing the association of this protein with the cytoskeleton. No significant differences in the localization of alpha-, beta-, or p120-catenins were detected under the three different conditions. 2. Dysfunction of E-cadherin can be reversed by incubation of HT-29 cells with the tyrosine kinase inhibitor herbimycin A. On the other hand an augmentation of c-src activity in HT-29 cells or HT-29 M6 cells treated with PMA was observed with respect to control HT-29 M6 cells. The phosphorylation status of catenins was also investigated; in HT-29 or in HT-29 M6 cells treated with PMA, dysfunction of E-cadherin was accompanied by an increased phosphorylation of p120-catenin and by an elevated association of this protein to E-cadherin. These results suggest a role for pp60src and the pp60src substrate p120-catenin in the control of E-cadherin function in HT-29 cells.

Full Text

The Full Text of this article is available as a PDF (310K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gumbiner B, Simons K. A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide. J Cell Biol. 1986 Feb;102(2):457–468. [PMC free article] [PubMed]
  • Takeichi M. Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem. 1990;59:237–252. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993 Sep;9(9):317–321. [PubMed]
  • Reynolds AB, Daniel J, McCrea PD, Wheelock MJ, Wu J, Zhang Z. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol Cell Biol. 1994 Dec;14(12):8333–8342. [PMC free article] [PubMed]
  • Lesuffleur T, Barbat A, Dussaulx E, Zweibaum A. Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells. Cancer Res. 1990 Oct 1;50(19):6334–6343. [PubMed]
  • Hafez MM, Infante D, Winawer S, Friedman E. Transforming growth factor beta 1 acts as an autocrine-negative growth regulator in colon enterocytic differentiation but not in goblet cell maturation. Cell Growth Differ. 1990 Dec;1(12):617–626. [PubMed]
  • Lesuffleur T, Barbat A, Luccioni C, Beaumatin J, Clair M, Kornowski A, Dussaulx E, Dutrillaux B, Zweibaum A. Dihydrofolate reductase gene amplification-associated shift of differentiation in methotrexate-adapted HT-29 cells. J Cell Biol. 1991 Dec;115(5):1409–1418. [PMC free article] [PubMed]
  • Fabre M, García de Herreros A. Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin. J Cell Sci. 1993 Oct;106(Pt 2):513–521. [PubMed]
  • Nagafuchi A, Ishihara S, Tsukita S. The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules. J Cell Biol. 1994 Oct;127(1):235–245. [PMC free article] [PubMed]
  • Hinck L, Näthke IS, Papkoff J, Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. [PMC free article] [PubMed]
  • Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA. Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem. 1986 Oct 15;261(29):13754–13759. [PubMed]
  • Kinch MS, Clark GJ, Der CJ, Burridge K. Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia. J Cell Biol. 1995 Jul;130(2):461–471. [PMC free article] [PubMed]
  • Shore EM, Nelson WJ. Biosynthesis of the cell adhesion molecule uvomorulin (E-cadherin) in Madin-Darby canine kidney epithelial cells. J Biol Chem. 1991 Oct 15;266(29):19672–19680. [PubMed]
  • Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Miyazawa K, Kitamura N, Johnson KR, Wheelock MJ, Matsuyoshi N, Takeichi M, et al. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol. 1995 Mar;128(5):949–957. [PMC free article] [PubMed]
  • Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM, Birchmeier W. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol. 1993 Feb;120(3):757–766. [PMC free article] [PubMed]
  • Uehara Y, Murakami Y, Sugimoto Y, Mizuno S. Mechanism of reversion of Rous sarcoma virus transformation by herbimycin A: reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60v-src1. Cancer Res. 1989 Feb 15;49(4):780–785. [PubMed]
  • Garcia R, Parikh NU, Saya H, Gallick GE. Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines. Oncogene. 1991 Nov;6(11):1983–1989. [PubMed]
  • Reynolds AB, Roesel DJ, Kanner SB, Parsons JT. Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol. 1989 Feb;9(2):629–638. [PMC free article] [PubMed]
  • Reynolds AB, Herbert L, Cleveland JL, Berg ST, Gaut JR. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo. Oncogene. 1992 Dec;7(12):2439–2445. [PubMed]
  • Peifer M, Berg S, Reynolds AB. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994 Mar 11;76(5):789–791. [PubMed]
  • Downing JR, Reynolds AB. PDGF, CSF-1, and EGF induce tyrosine phosphorylation of p120, a pp60src transformation-associated substrate. Oncogene. 1991 Apr;6(4):607–613. [PubMed]
  • Lee H, Hsu S, Winawer S, Friedman E. Signal transduction through extracellular signal-regulated kinase-like pp57 blocked in differentiated colon carcinoma cells having low levels of c-src kinase. J Biol Chem. 1993 Apr 15;268(11):8181–8187. [PubMed]
  • Hamaguchi M, Matsuyoshi N, Ohnishi Y, Gotoh B, Takeichi M, Nagai Y. p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system. EMBO J. 1993 Jan;12(1):307–314. [PMC free article] [PubMed]
  • García de Herreros A, Fabre M, Batlle E, Balagué C, Real FX. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate blocks differentiation of HT-29 human colon cancer cells. J Cell Sci. 1993 Aug;105(Pt 4):1165–1172. [PubMed]
  • Herrera R, Lebwohl D, Garcia de Herreros A, Kallen RG, Rosen OM. Synthesis, purification, and characterization of the cytoplasmic domain of the human insulin receptor using a baculovirus expression system. J Biol Chem. 1988 Apr 25;263(12):5560–5568. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...