Role of CrkII in Fc gamma receptor-mediated phagocytosis
Abbreviated Journal Title
J. Biol. Chem.
NUCLEOTIDE EXCHANGE FACTORS; ADAPTER PROTEINS; APOPTOTIC CELLS; RHO-GTPASES; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHATIDYLSERINE RECEPTOR; RAC-GEF; ACTIVATION; MEMBRANE; COMPLEX; Biochemistry & Molecular Biology
Phagocytosis of IgG-opsonized pathogens by Fc gamma receptors requires extensive remodeling of the actin cytoskeleton, a process regulated by the small GTPase Rac. Vav was thought to be the guanine nucleotide exchange factor responsible for the activation of Rac, but recent evidence indicates that Fc gamma receptor-mediated phagocytosis is unaffected in macrophages lacking all three isoforms of Vav. We therefore tested whether another GEF, DOCK180, participates in Fc gamma receptor-initiated phagocytosis. DOCK180 associates with the adaptor protein Crk, which mediates recruitment of the GEF to sites of tyrosine phosphorylation. CrkII and DOCK180 were found to accumulate at the phagocytic cup. Knockdown of Crk or DOCK180 in murine macrophages using small interfering RNA inhibited phagocytosis of IgG-opsonized particles. Moreover, transfection of dominant negative CrkII prevented both recruitment of DOCK180 and the activation of Rac at the phagocytic cup. This is the first report of a role for either Crk or DOCK180 in Fc gamma receptor-mediated phagocytosis. The Crk-DOCK180 complex is involved in the clearance of apoptotic cells, which unlike the ingestion of IgG-opsonized particles, is an anti-inflammatory process. The finding that CrkII-DOCK180 is also responsible, at least in part, for the effects of Fc gamma receptors implies that additional, parallel pathways must account for the associated pro-inflammatory effect.
Journal of Biological Chemistry
"Role of CrkII in Fc gamma receptor-mediated phagocytosis" (2007). Faculty Bibliography 2000s. 7345.