Identification of Peptide and Protein Ligands for the Caveolin-scaffolding Domain. IMPLICATIONS FOR THE INTERACTION OF CAVEOLIN WITH CAVEOLAE-ASSOCIATED PROTEINS (original) (raw)

Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes. We have suggested that caveolin functions as a scaffolding protein to organize and concentrate certain caveolin-interacting proteins within caveolae membranes. In this regard, caveolin co-purifies with a variety of lipid-modified signaling molecules, including G-proteins, Src-like kinases, Ha-Ras, and eNOS. Using several independent approaches, it has been shown that a 20-amino acid membrane proximal region of the cytosolic amino-terminal domain of caveolin is sufficient to mediate these interactions. For example, this domain interacts with G-protein ␣ subunits and Src-like kinases and can functionally suppress their activity. This caveolinderived protein domain has been termed the caveolinscaffolding domain. However, it remains unknown how the caveolin-scaffolding domain recognizes these molecules.