title: Critical phosphorylation sites for acetyl-CoA carboxylase activity.
abstract: Acetyl-CoA carboxylase (ACC) is rapidly regulated by reversible phosphorylation; phosphorylation inactivates ACC, whereas dephosphorylation activates the enzyme. Among protein kinases only cAMP-dependent protein kinase and 5'-AMP-dependent protein kinase can inactivate ACC; cAMP-dependent protein kinase phosphorylates Ser-77 and -1200; 5'-AMP-dependent protein kinase phosphorylates Ser-79, -1200, and -1215. In this report, the construction and expression of ACC cDNA containing the entire coding region (7.2 kilobase pairs) is described. In order to identify the critical phosphorylation site(s) for each protein kinase, we introduced site-specific mutations at Ser-77, -79, -1200, and -1215 of ACC cDNA and a series of mutated ACCs containing various combinations of these four mutated sites was expressed. By examination of the various mutant ACCs, we provided evidence that the effect of cAMP-dependent protein kinase is entirely mediated by the phosphorylation of Ser-1200 and that Ser-79 is important for 5'-AMP-dependent protein kinase action in vitro.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.
authors.forename: J
authors.initials: J
authors.lastname: Ha
authors.forename: S
authors.initials: S
authors.lastname: Daniel
authors.forename: S S
authors.initials: SS
authors.lastname: Broyles
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation
chemical_list: D018076:DNA, Complementary; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000103:Acetyl-CoA Carboxylase