Cbl Associates with Pyk2 and Src to Regulate Src Kinase Activity, αvβ3 Integrin-Mediated Signaling, Cell Adhesion, and Osteoclast Motility

摘要: The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts transfected 293 cells, we find a molecular complex comprising Src, Pyk2, Cbl functions to adhesion motility. activation integrin αvβ3 induces the [Ca2+]i-dependent phosphorylation Pyk2 Y402, its association with Src SH2, activation, SH3-dependent recruitment c-Cbl. Furthermore, PTB domain is shown bind phosphorylated Tyr-416 in loop autophosphorylation site inhibiting kinase activity integrin-mediated adhesion. Finally, show deletion c or c-Cbl leads decrease osteoclast migration. Thus, binding formation Pyk2/Src/Cbl which key regulator These findings may explain osteopetrotic phenotype Src−/− mice.