title: ACTH-dependent proteolytic activity of a novel phosphoprotein (p43) intermediary in the activation of phospholipase A2 and steroidogenesis.
abstract: Arachidonic acid (AA) and the lipooxygenase products have been shown to play an obligatory role in the mechanism of action of LH and ACTH, at a point after cAMP-dependent phosphorylation. We have demonstrated the presence of a phosphoprotein (p43) that responds to cAMP signals to induce steroid synthesis in adrenocortical tissue, an effect that is blocked by phospholipase A2 inhibitors. In this report we demonstrate that p43 exhibits autoproteolytic activity that is regulated by ACTH. Protein purified from ACTH-treated animals exhibited degradation in some of the isoforms resolved on two dimensional gel electrophoresis. Proteinase inhibitors (PMSF and 1,10 phenantroline) inhibited steroid synthesis induced by ACTH and 8-Br-cAMP in intact cells. Addition of exogenous AA reverted in part that inhibition. Here we present evidence for a hormone-regulated proteolytic activity of p43 and for the inhibition of steroidogenesis by proteinase inhibitors acting prior to the release of arachidonic acid.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Buenos Aires, Argentina.
authors.forename: C B
authors.initials: CB
authors.lastname: Cymeryng
authors.forename: C
authors.initials: C
authors.lastname: Paz
authors.forename: L
authors.initials: L
authors.lastname: Dada
authors.forename: F
authors.initials: F
authors.lastname: Cornejo Maciel
authors.forename: M I
authors.initials: MI
authors.lastname: Neuman
authors.forename: P G
authors.initials: PG
authors.lastname: Mele
authors.forename: C
authors.initials: C
authors.lastname: Finkielstein
authors.forename: A R
authors.initials: AR
authors.lastname: Solano
authors.forename: C F
authors.initials: CF
authors.lastname: Mendez
authors.forename: M
authors.initials: M
authors.lastname: Park
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation; D006868:Hydrolysis; D024101:Mitochondrial Proteins; D010170:Palmitoyl-CoA Hydrolase; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013256:Steroids / Q000096:biosynthesis*; D013869:Thiolester Hydrolases
chemical_list: D024101:Mitochondrial Proteins; D011506:Proteins; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D010741:Phospholipases A; D054467:Phospholipases A2; D013869:Thiolester Hydrolases; C546434:Acot2 protein, rat; D010170:Palmitoyl-CoA Hydrolase