title: Phospholipids inhibit proteolysis of protein kinase C alpha by mM calcium-requiring calpain.
abstract: The alpha isoform of protein kinase C (PKC alpha) is rapidly hydrolyzed by mM Ca(2+)-requiring calpain (calcium-activated neutral proteinase) under cell-free conditions (Shea et al, 1994, FEBS Lett. 350:223). In the present study, we demonstrate that this hydrolysis is inhibited by phosphatidyl serine, diacylglycerol, phosphatidyl choline, phosphatidyl inositol, and phosphatidic acid. With the exception of phosphatidic acid, these phospholipids did not directly inhibit calpain activity as evidenced by degradation of [14C]azocasein, suggesting that the nature of inhibition of calpain-mediated PKC alpha degradation is due to an effect of phospholipids on PKC alpha conformation. These findings suggest that m calpain-mediated PKC alpha hydrolysis may be specifically minimized at the plasma membrane, and leave open the possibility that such a mechanism exists in situ. In addition, the unique inhibition of calpain activity by phosphatidic acid suggests the existence of a specific mechanism by which this phospholipid regulates PKC alpha activity.
authors.affiliation: Centre de Neurochimie du CNRS, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Lang
authors.forename: M L
authors.initials: ML
authors.lastname: Beermann
authors.forename: G
authors.initials: G
authors.lastname: Hauser
authors.forename: C M
authors.initials: CM
authors.lastname: Cressman
authors.forename: T B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D002154:Calpain / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D010743:Phospholipids / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051571:Protein Kinase C-alpha
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010743:Phospholipids; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D002154:Calpain