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A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase.

Caveolin-1 is a substrate for nonreceptor tyrosine kinases including Src, Fyn, and Abl. To investigate the function of caveolin-1 phosphorylation, we modified the Gal4-based yeast two-hybrid system to screen for phosphorylation-dependent protein interactions. A cDNA library was screened using the N terminus of caveolin-1 as bait in a yeast strain expressing the catalytic domain of Abl. We identified two proteins in this screen that interact with caveolin-1 in a phosphorylation-dependent manner: tumor necrosis factor-alpha receptor-associated factor 2 (TRAF2) and C-terminal Src kinase (Csk). TRAF2 bound to nonphosphorylated caveolin-1, but this association was increased 3-fold by phosphorylation. In contrast, association of Csk with caveolin-1 was completely dependent on phosphorylation of caveolin-1, both for fusion proteins in yeast (>35-fold difference in affinity) and for endogenous proteins in tissue culture cells. Our data suggest that phosphorylation of caveolin-1 leads to Csk translocation into caveolae. This may induce a feedback loop that leads to inactivation of the Src family kinases that are highly enriched in caveolae.

Pubmed ID: 11805080

Authors

  • Cao H
  • Courchesne WE
  • Mastick CC

Journal

The Journal of biological chemistry

Publication Data

March 15, 2002

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK56197

Mesh Terms

  • 3T3 Cells
  • Animals
  • Biological Transport
  • Caveolin 1
  • Caveolins
  • Mice
  • Phosphorylation
  • Protein-Tyrosine Kinases
  • Proteins
  • TNF Receptor-Associated Factor 2
  • Tyrosine
  • src-Family Kinases