Caveolin is an inhibitor of platelet-derived growth factor receptor signaling

Exp Cell Res. 1999 Mar 15;247(2):380-8. doi: 10.1006/excr.1998.4379.

Abstract

Caveolin is a major structural component of caveolae and has been implicated in the regulation of the function of several caveolae-associated signaling molecules. Platelet-derived growth factor (PDGF) receptors and caveolin were colocalized in the same subcellular fraction after sucrose density gradient fractionation of fibroblasts. Additionally, we found that the PDGF receptors interacted with caveolin in NIH3T3 fibroblast cells. We then examined whether caveolin directly binds to PDGF receptors and inhibits kinase activity using a recombinant PDGF receptor overexpressed in insect cells and peptides derived from the scaffolding domain of caveolin subtypes. We found the peptide from caveolin-1 and -3, but not -2, inhibited the autophosphorylation of PDGF receptors in a dose-dependent manner. Similarly, caveolin-1 and -3 peptides directly bound to PDGF receptors. Mutational analysis using a series of truncated caveolin-3 peptides (20-, 17-, 14-, and 11-mer peptides) revealed that at least 17 amino acid residues of the peptide were required to inhibit and directly bind to PDGF receptors. Thus, our findings suggest that PDGF receptors directly interact with caveolin subtypes, leading to the inhibition of kinase activity. Caveolin may be another regulating factor of PDGF-mediated tyrosine kinase signaling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Caveolin 1
  • Caveolins*
  • Cell Fractionation
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphorylation
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Signal Transduction*

Substances

  • CAV1 protein, human
  • Cav1 protein, mouse
  • Caveolin 1
  • Caveolins
  • Membrane Proteins
  • Receptors, Platelet-Derived Growth Factor