Convergence of αvβ3Integrin–And Macrophage Colony Stimulating Factor–Mediated Signals on Phospholipase Cγ in Prefusion Osteoclasts

摘要: The macrophage colony stimulating factor (M-CSF) and alpha(v)beta(3) integrins play critical roles in osteoclast function. This study examines M-CSF- adhesion-induced signaling prefusion osteoclasts (pOCs) derived from Src-deficient wild-type mice. cells attach to but do not spread on vitronectin (Vn)-coated surfaces and, contrary cells, their adhesion does lead tyrosine phosphorylation of molecules activated by adhesion, including PYK2, p130(Cas), paxillin, PLC-gamma. However, response M-CSF, Src(-/-) pOCs migrate Vn an alpha(v)beta(3)-dependent manner. Involvement PLC-gamma activation is suggested using a PLC inhibitor, U73122, which blocks both adhesion- M-CSF-mediated cell spreading. Furthermore, together with filamentous actin, causes recruitment beta(3) integrin contacts induces stable association PLC-gamma, phosphatidylinositol 3-kinase, PYK2. Moreover, direct interaction PYK2 can be induced either or suggesting that this may enable the formation integrin-associated complexes. suggests common downstream mediator for growth signals. M-CSF-initiated modulates integrin-mediated cytoskeletal reorganization absence c-Src, possibly via