Actin polymerization drives the extension of pseudopods required for phagocytosis. @entity1078 ( @entity1078 ) is thought to play a central role in this process, because it interacts with several actin-regulatory proteins and undergoes acute and localized changes at sites of phagocytosis. We therefore studied whether @entity1076 5-kinase (PIPK), the enzyme responsible for the generation of @entity1078 from @entity1076 , is involved in the control of phagocytosis. PIPKIalpha was found to accumulate transiently on forming phagosomes. To test the functional involvement of PIPKIalpha in particle engulfment, we generated a double mutant ( @entity70540 / @entity70541 ) that lacks kinase activity. When ectopically expressed in cultured cells, this mutant is targeted to the plasma membrane and accumulates at the phagosomal cup during particle engulfment. Expression of PIP5KIalpha @entity70540 / @entity70541 impaired phagocytosis in RAW264.7 macrophages and in engineered phagocytes generated by transfection of Fc receptors in @entity3569 ovary cells. Inhibition of phagocytosis could not be attributed to defects in particle binding or receptor clustering, which was monitored using green fluorescent protein-tagged Fcgamma receptors. Instead, expression of the inactive kinase diminished the accumulation of @entity1078 and of F-actin in the phagosomal cup. These data suggest that PIPKIalpha activity is involved in the actin remodeling that is a prerequisite for efficient phagocytosis. PIPKIalpha appears to contribute to the transient changes in PIP(2) levels that are associated with, and likely required for, the recruitment and regulation of actin-modulating proteins.

Inhibition of XXXX 5-kinase Ialpha impairs localized actin remodeling and suppresses phagocytosis.

@entity1078 :: ('CHEBI:18348', 'Chemical') :: ['PIP(2)', 'Phosphatidylinositol 4,5-bisphosphate'] @entity70541 :: ('p|SUB|R|427|Q', 'ProteinMutation') :: ['R427Q'] @entity1076 :: ('MESH:C037178', 'Chemical') :: ['phosphatidylinositol-4-phosphate', 'phosphatidylinositol 4-phosphate'] @entity70540 :: ('p|SUB|D|309|N', 'ProteinMutation') :: ['D309N'] @entity3569 :: ('10029', 'Species') :: ['Chinese hamster']
@entity1076 :: (MESH:C037178,Chemical) :: ['phosphatidylinositol-4-phosphate']
