Regulation of type II alpha phosphatidylinositol phosphate kinase localisation by the protein kinase CK2

Inositol lipid synthesis is regulated by several distinct families of enzym es [1], Members of one of these families, the type II phosphatidylinositol phosphate kinases (PIP kinases), are I-kinases and are thought to catalyse a minor route of synthesis of the multifunctional phosphatidylinositol 4,5- bisphosphate (PI(4,5)P-2) from the inositide PI(5)P [2]. Here, we demonstra te the partial purification of a protein kinase that phosphorylates the typ e II alpha PIP kinase at a single site unique to that isoform - Ser304, Thi s kinase was identified as protein kinase CK2 (formerly casein kinase 2). M utation of Ser304 to aspartate to mimic its phosphorylation had no effect o n PIP kinase activity, but promoted both redistribution of the green fluore scent protein (GFP)-tagged enzyme in HeLa cells from the cytosol to the pla sma membrane, and membrane ruffling. This effect was mimicked by mutation o f Ser304 to alanine, although not to threonine, suggesting a mechanism invo lving the unmasking of a latent membrane localisation sequence in response to phosphorylation.