Intracellular Activation of Protein Kinase C and Regulation of the Surface Transferrin Receptor by Diacylglycerol is a Spontaneously Reversible Process That is Associated with Rapid Formation of Phosphatidic Acid

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 5; pp. 1281 - 1284
• Main Authors: May, W. Stratford, Lapetina, Eduardo G., Cuatrecasas, Pedro
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.03.1986; National Acad Sciences
• Subjects: Biological and medical sciences; Calcimycin - pharmacology; Cell receptors; Cell structures and functions; Chromatography; Diglycerides; Diglycerides - pharmacology; Down regulation; Drug Synergism; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Glycerides - pharmacology; Humans; Molecular and cellular biology; Phorbol esters; Phosphatidic acids; Phosphatidic Acids - physiology; Phospholipids; Phosphorylation; Protein Kinase C - metabolism; Protein metabolism; Receptors; Receptors, Cell Surface - metabolism; Receptors, Transferrin; Transferrin receptors; Human origin; Cell culture; Regulation(control); Transferrin; Diglyceride; Protein kinase; Internalization; Activation; Intracellular; Phosphatidic acid; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.5.1281

The effect of the synthetic diacylglycerol, sn-1,2-dioctanoylglycerol (diC8), on the expression of the surface transferrin receptor reveals that exogenous diC8 can act as an intracellular activator of protein kinase C and stimulate both down-regulation and increased receptor phosphorylation in a manner similar to that induced by the active tumor promotor, 4β -phorbol 12,13-dibutyrate. Unlike the spontaneously irreversible effect noted when 4β -phorbol 12,13-dibutyrate is added, this same effect mediated by diC8 is brief, lasting only minutes, and is spontaneously reversible. The rate of reversibility is dependent on the concentration of diC8 added, and it is associated with rapid formation of a newly detected intracellular phospholipid that corresponds to sn-1,2-dioctanoyl phosphatidic acid. These data, in conjunction with findings that demonstrate that exogenous diacylglycerols (including diC8 when added to cells do not stimulate cellular phospholipase A2 or C, argue that protein kinase C is activated only briefly in this system since exogenous diC8 is subject to rapid intracellular metabolism to phosphatidic acid.