title: Casein kinase I is regulated by phosphatidylinositol 4,5-bisphosphate in native membranes.
abstract: Casein kinase I activity is present in cells as a cytosolic and a membrane-bound enzyme. Previously, the erythroid membrane-bound casein kinase I was shown to associate with purified integral membrane proteins; this association and protein kinase activity was regulated by phosphatidylinositol 4,5-bisphosphate (PIP2) (Bazenet, C.E., Brockman, J.L., Lewis, D., Chan, C., and Anderson, R.A. (1990) J. Biol. Chem. 265, 7369-7376). Here we show that both the membrane-bound and the cytosolic casein kinase interact with native membranes and that this interaction is regulated by the membrane content of PIP2. On native membranes, casein kinase I activity is potently inhibited by small increases (10-20%) in the membrane content of either exogenously added or intrinsic PIP2. However, the majority of the intrinsic content of PIP2 in isolated membranes does not inhibit casein kinase, suggesting that this PIP2 is not accessible. Regulation of the casein kinases on membranes is sensitive to detergents and to chymotrypsin treatment of membranes.
authors.affiliation: Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
authors.forename: J L
authors.initials: JL
authors.lastname: Brockman
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D047388:Casein Kinases; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology*; D002918:Chymotrypsin / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D003902:Detergents; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D003902:Detergents; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D047388:Casein Kinases; D002918:Chymotrypsin