Activation of the p21 pathway of growth arrest and apoptosis by the β4 integrin cytoplasmic domain

A. S. Clarke, M. M. Lotz, C. Chao, A. M. Mercurio

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

The integrin α6β4, a receptor for members of the laminin family of basement membrane components, contributes to the function of epithelial cells and their oncogenically transformed derivatives. In our efforts to study α6β4-mediated functions in more detail and to assess the contribution of the β4 cytoplasmic domain in such functions, we identified a rectal carcinoma cell line that lacks expression of the β4 integrin subunit. This cell line, termed RKO, expresses α6β1 but not α6β4, and it interacts with laminin-1 less avidly than similar cell lines that express α6β4. We expressed a full-length β4 cDNA, as well as a mutant cDNA that lacks the β4 cytoplasmic domain, in RKO cells and isolated stable subclones of these transfectants. In this study, we report that subclones that expressed the full-length β4 cDNA in association with endogenous α6 exhibited partial G1 arrest and apoptosis, properties that were not evident in RKO cells transfected with either the cytoplasmic domain mutant or the expression vector alone. In an effort to define a mechanism for these observed changes in growth, we observed that expression of the α6β4 integrin induced expression of the p21 (WAF1; CiP1) protein, an inhibitor of cyclin-dependent kinases. These data suggest that the β4 integrin cytoplasmic domain is linked to a signaling pathway involved in cell cycle regulation in the β4 transfected RKO cells.

Original languageEnglish (US)
Pages (from-to)22673-22676
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number39
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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