Effect of protein kinase C on endoplasmic reticulum cholesterol.
Plasma membrane cholesterol both regulates and is regulated by effector proteins in the endoplasmic reticulum (ER) through a feedback system that is poorly understood. We now show that ER cholesterol varies over a fivefold range in response to experimental agents that act upon protein kinase C (PKC). Agents that activate Ca(2+)-dependent PKC [phorbol-12-myristate-13-acetate (PMA) and bryostatin 1] increased the level of ER cholesterol; inhibitors such as staurosporine and calphostin C decreased it. Rottlerin, a selective inhibitor of the PKC-delta isoform, also increased ER cholesterol. The esterification of plasma membrane cholesterol was altered by protein kinase C-directed agents in a corresponding fashion. Furthermore, the regulatory effect of plasma membrane cholesterol on the esterification of ER cholesterol was blocked by PKC-directed agents. These findings suggest that multiple protein kinase C isoforms participate in the regulation of ER cholesterol and therefore in cholesterol homeostasis.
Lange
Yvonne
Y
Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA. ylange@rush.edu
Ye
Jin
J
Steck
Theodore L
TL
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D054713:Bryostatins; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008934:Mitogens / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000098:Acetophenones; D001578:Benzopyrans; D054713:Bryostatins; D004791:Enzyme Inhibitors; D007783:Lactones; D018942:Macrolides; D008934:Mitogens; D009281:Naphthalenes; D020033:Protein Isoforms; C046785:bryostatin 1; D002784:Cholesterol; C085746:rottlerin; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium