title: Long-chain acyl-CoA synthetase 4 is regulated by phosphorylation.
abstract: Long chain acyl CoA synthetase 4 (Acsl4) is a key enzyme in steroidogenesis. It participates in steroid synthesis through of arachidonic acid release and Steroidogenic Acute Regulatory protein (StAR) induction. Acsl4 prefers arachidonic acid as substrate and acts probably as a homodimer. In steroidogenic cells, it has been demonstrated that Acsl4 is a high turnover protein located mainly in mitochondrial-associated membrane fraction (MAM) bound to other proteins and that it is newly synthesized by hormone stimulation. The synthesis of Acsl4 constitutes an early step in steroidogenesis. In the steroid synthesis process, activation of kinases plays a very important role. For this reason, the aim of this work was to study Acsl4 as a possible phosphoprotein and try to elucidate the role of its phosphorylation. We have determined for the first time that Acsl4 is a phosphoprotein whose phosphorylation is hormone-dependent. We also demonstrated that Acsl4 acts effectively as a dimer and that phosphorylation occurs after dimer formation. Studies in vitro demonstrated that Acsl4 is a substrate of both PKA and PKC and its phosphorylation by these kinases regulates its activity.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Buenos Aires, CONICET, Buenos Aires, Argentina.
authors.forename: María Emilia
authors.initials: ME
authors.lastname: Smith
authors.forename: G Ezequiel
authors.initials: GE
authors.lastname: Saraceno
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
authors.forename: Rocío
authors.initials: R
authors.lastname: Castilla
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003066:Coenzyme A Ligases / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013379:Substrate Specificity; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C581020:Acsl4 protein, mouse; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase