Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase

Nature. 1996 Jan 4;379(6560):91-6. doi: 10.1038/379091a0.

Abstract

The interaction of cells with the extracellular matrix regulates cell shape, motility, growth, survival, differentiation and gene expression, through integrin-mediated signal transduction. We used a two-hybrid screen to isolate genes encoding proteins that interact with the beta 1-integrin cytoplasmic domain. The most frequently isolated complementary DNA encoded a new, 59K serine/threonine protein kinase, containing four ankyrin-like repeats. We report here that this integrin-linked kinase (ILK) phosphorylated a beta 1-integrin cytoplasmic domain peptide in vitro and coimmunoprecipitated with beta 1 in lysates of mammalian cells. Endogenous ILK kinase activity was reduced in response to fibronectin. Overexpression of p59ILK disrupted epithelial cell architecture and inhibited adhesion to integrin substrates, while inducing anchorage-independent growth. We propose that ILK is a receptor-proximal protein kinase regulating integrin-mediated signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Base Sequence
  • Cell Adhesion*
  • Cell Division*
  • Cell Line
  • DNA, Complementary
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism
  • Humans
  • Integrin beta1 / metabolism*
  • Molecular Sequence Data
  • Myelin Basic Protein / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Antibodies
  • DNA, Complementary
  • Fibronectins
  • Integrin beta1
  • Myelin Basic Protein
  • Recombinant Fusion Proteins
  • integrin-linked kinase
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/U40282