title: Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity.
abstract: 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.
authors.affiliation: Division of Nephrology, Jewish Hospital/Washington University Medical Center, St. Louis, Missouri 63110, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Hruska
authors.forename: F
authors.initials: F
authors.lastname: Rolnick
authors.forename: M
authors.initials: M
authors.lastname: Huskey
authors.forename: U
authors.initials: U
authors.lastname: Alvarez
authors.forename: D
authors.initials: D
authors.lastname: Cheresh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002645:Chickens; D005260:Female; D007163:Immunosorbent Techniques; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016023:Integrins; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D015688:Oncogene Protein pp60(v-src)