ENGAGEMENT OF THE OSTEOCLAST INTEGRIN ALPHA(V)BETA(3) BY OSTEOPONTIN STIMULATES PHOSPHATIDYLINOSITOL 3-HYDROXYL KINASE-ACTIVITY

Osteoclast adhesion via integrin alpha(v) beta(3) to the bone matrix protein osteopontin (OPN) results in stimulation of bone resorption. We characterized an immediate signaling event that takes place upon osteoclast interaction with OPN. OPN binding to alpha(v) beta(3) results in the rapid production of the phosphoinositides (PtdInsP), including phosphatidylinositol triphosphate (PtdIns 3,4,5P(3)). Stimulation of 3,4,5-PtdInsP(3) production by OPN was produced by increased activity of PtdInsP 3-OH kinase, which was found in immunoprecipitates formed by antibodies to integrin alpha(v) beta(3). The association of PtdIns 3-OH kinase with integrin may have been through association with c-src. The latter was present in immunoprecipitates formed by the antibodies to integrin alpha(v) beta(3), and src kinase was activated by OPN. These findings demonstrate a mechanism for rapid generation of cell signals upon matrix protein binding to alpha(v) beta(3), which resembles the mechanisms used by tyrosine kinase growth factor receptors.