Phosphatidylinositol-4-phosphate 5-kinase-1β is essential for epidermal growth factor receptor-mediated endocytosis

Phosphatidylinositol-4,5-bisphosphate (PIP2) is known to play an important role in signal transduction and membrane trafficking. We show that one enzyme responsible for PIP2 production, phosphatidylinositol-4-phosphate 5-kinase type 1 beta (PIPK beta), is essential for epidermal growth factor receptor (EGFR)-mediated endocytosis. Expression of murine PIPK beta in NR6 cells expressing EGFR strikingly increased receptor internalization. Moreover, the kinase was shown to form an immunoprecipitable complex with EGFR. Expression of either a truncated kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the membrane recruitment of PIPK beta and both clathrin light chain and dynamin. Our results delineate a novel mechanism by which PIPK beta regulates receptor-mediated endocytosis and receptor tyrosine kinase membrane traffic.