PLCβ1-mediated hydrolysis of PIP2 is inhibited by the focal adhlsion protein vinculin

L. Petch, K. Burridge

Research output: Contribution to journalArticle

Abstract

Adhesion of cells to the extracellular matrix is required for the growth and proliferation of most normal cells, a property known as anchorage dependence of growth. Previous studies have shown that changes in the levels of expression of the focal adhesion protein vinculin are correlated with anchorage-dependent cell growth. For example, SV40-transformed Balb/c3T3 cells exhibit reduced levels of vinculin expression and are anchorage independent. Transfection of a vinculin cDNA into these cells supresses their anchorage independent growth and tumorigenic ability. Similar results have been obtained with α-actinin. The mechanism whereby changes in vinculin or α-actinin expression alter anchorage-dependent cell growth is not clear. A number of actin-binding proteins, including vinculin and α-actinin, bind to and are regulated by phosphatidylinositol 4,5-hisphosphate (PIP2) Two of these, profilin and gelsolin, have been shown to inhibit phospholipase C (PLC)-mediated hydrolysis of PIP2, Given these data, we hypothesize that the effect of vinculin on anchorage dependent growth is due to its ability to bind PIP2. Consistent with this, we have shown in three separate experiments that intact vinculin inhibits PLCβ1-mediated PIP2 hydrolysis in vitro. This inhibition was dose-dependent and maximal at 20μM vinculin. The PIP2 binding site ot vinculin has been mapped to a 32 kDa C-termmal tail fragment of the protein. Experiments are underway to determine whether the effects of intact vinculin on PLCβ1 can be mimicked by the tail fragment alone. The effects of vinculin expression levels on PIP2 hydrolysis are also being tested in vivo.

Original languageEnglish (US)
Pages (from-to)A311
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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