A Regulatory Role for Src Homology 2 Domain–Containing Inositol 5′-Phosphatase (Ship) in Phagocytosis Mediated by Fcγ Receptors and Complement Receptor 3 (αMβ2; Cd11b/Cd18)

摘要: The Src homology 2 domain–containing inositol 5′-phosphatase (SHIP) is recruited to immunoreceptor tyrosine-based inhibition motif (ITIM)–containing proteins, thereby suppressing phosphatidylinositol 3-kinase (PI 3-kinase)–dependent pathways. role of SHIP in phagocytosis, a PI 3-kinase–dependent pathway, unknown. Overexpression macrophages led an phagocytosis mediated by receptors for the Fc portion IgG (FcγRs). In contrast, expressing catalytically inactive or lacking expression demonstrated enhanced phagocytosis. To determine whether regulates that are not known recruit ITIMs, we determined effect on complement receptor 3 (CR3; CD11b/CD18; αMβ2)–dependent Macrophages overexpressing impaired CR3-mediated whereas derived from SHIP−/− mice was up 2.5 times as efficient observed littermate controls. localized FcγR- and CR3-containing phagocytic cups cytoskeleton upon clustering CR3. transfected COS cell model activation-independent active but also inhibited We conclude 3-kinase(s) regulate multiple forms endogenous plays modulating β2 integrin outside-in signaling.