Figure 7.

Model for regulation of β1 integrin signaling by caveolin. The model indicates that caveolin binds and maintains Src family kinases in an inactive configuration (dark shade) proximate to a fraction of β1 integrins (complex is encircled). Whether these complexes exists in caveolae as signaling units or separately from caveolae is currently unknown (see text). Ligand engagement of integrins and clustering of caveolin along with integrins results in homo-oligomerization of caveolin and release of Src kinases from caveolin. This in turn allows Src kinases to activate (light shade) through a phosphatase and/or through direct binding to substrates at the developing focal contact site. Available evidence suggests that Fyn kinase may primarily function in MAPK activation whereas Src/Yes may primarily function to activate FAK and phosphorylate other cytoskeletal proteins leading to the organization and development of an adhesion plaque. The model also proposes that as integrins activate in response to ligand-induced clustering, uPAR moves into the complexes enriching them with caveolin and its associated signaling molecules. The importance of uPAR, when present, to the complexes is illustrated by the ability of uPAR-binding peptides to disrupt signaling through β1 integrins in SMC (Fig. 6).