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Endocrinology, Vol 136, 2984-2992, Copyright © 1995 by Endocrine Society

ARTICLES

Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity

KA Hruska, F Rolnick, M Huskey, U Alvarez and D Cheresh
Division of Nephrology, Jewish Hospital/Washington University Medical Center, St. Louis, Missouri 63110, USA.

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 3,4,5P3). Stimulation of 3,4,5-PtdInsP3 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.


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