Type Iγ phosphaticlylinositol phosphate kinase is required for EGF-stimulated directional cell migration

Phosphatidylinositol 4,5-bisphosphate (PI4,5P(2) modulates a plethora of cytoskeletal interactions that control the dynamics of actin assembly and, ultimately, cell migration. We show that the type Fy phosphaticlylinositol phosphate kinase 661 (PIPKI-y661), an enzyme that generates PI4,5P(2) , is required for growth factor but not G protein-coupled receptor-stimulated directional migration. By generating PI4,5P(2) and regulating talin assembly, PIPKI gamma 661 modulates nascent adhesion formation at the leading edge to facilitate cell migration. The epidermal growth factor (EGF) receptor directly phosphorylates PIPKI gamma 661 at tyrosine 634, and this event is required for EGF-induced migration. This phosphorylation regulates the interaction between PIPKI gamma 661 and phospholipase C gamma l (PLC gamma 1, an enzyme previously shown to be involved in the regulation of EGF-stimulated migration). Our results suggest that phosphorylation events regulating specific PIPKI gamma 661 interactions are required for growth factor induced migration. These interactions in turn define the spatial and temporal generation of PI4,5P(2) and derived messengers required for directional migration.