The subcellular localization control of integrin linked kinase 1 through its protein-protein interaction with caveolin-1

Cell Signal. 2005 Jun;17(6):751-60. doi: 10.1016/j.cellsig.2004.10.016. Epub 2004 Nov 23.

Abstract

Integrin linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been shown to be crucial for the cell survival, differentiation, and Wnt signaling. Firstly, by using a confocal microscopy and a transfection approach, we obtained the evidence that ILK1 interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. By ILK1 deletion mutant analysis, we characterized the caveolin-1-binding domain in the kinase domain of ILK1. In addition, we found that native ILK1 is associated with endogenous caveolin-1 in COS-1 cells. Secondly, transient transfection assays showed that a reduction in caveolin-1 binding leads to a substantial increase in the serine/threonine phosphorylation of ILK1. Thirdly, caveolin-1 and its scaffolding peptide (amino acids 82-101) functionally suppressed the auto-kinase activity of purified recombinant ILK1 protein. Fourthly, the association of ILK1 with caveolin-1 regulated its cytoplasmic retention; if it was not associated with caveolin-1, it was transported to the nucleus. Fifthly, we also noticed the putative nuclear localization sequences (nls) in ILK1 near the caveolin-1-binding domain. Thus, our data indicate that caveolin-1 regulates ILK1 auto-phosphorylation activity and its subcellular localization via a specific protein-protein interaction through blocking the exposure of its putative nls motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • COS Cells
  • Caveolin 1
  • Caveolins / metabolism*
  • Chlorocebus aethiops
  • Phosphorylation
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism*
  • Serine / metabolism

Substances

  • Caveolin 1
  • Caveolins
  • Serine
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases