Type IIalpha phosphatidylinositol phosphate kinase associates with the plasma membrane via interaction with type I isoforms.
The phosphatidylinositol phosphate kinases (PIPkins) are a family of enzymes involved in regulating levels of several functionally important inositol phospholipids within cells. The PIPkin family is subdivided into three on the basis of substrate specificity, each subtype presumably regulating levels of different subsets of the inositol lipids. The physiological function of the type II isoforms, which exhibit a preference for phosphatidylinositol 5-phosphate, a lipid about which very little is known, is particularly poorly understood. In the present study, we demonstrate interaction between, and co-immunoprecipitation of, type IIalpha PIPkin with the related, but biochemically and immunologically distinct, type I PIPkin isoforms. Type IIalpha PIPkin interacts with all three known type I PIPkins (alpha, beta and gamma), and in each case co-expression of the type I isoform with type IIalpha results in recruitment of the latter from the cytosol to the plasma membrane of the cell. This change in subcellular localization could result in improved access of the type IIalpha PIPkin to its lipid substrates.
Hinchliffe
Katherine A
KA
University of Cambridge, Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, U.K. kah224@cam.ac.uk
Giudici
Maria Luisa
ML
Letcher
Andrew J
AJ
Irvine
Robin F
RF
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D016297:Mutagenesis, Site-Directed; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D013552:Swine
D015778:Minor Histocompatibility Antigens; D001224:Aspartic Acid; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; D008239:Lysine