Acetyl-CoA carboxylase mRNA species with or without inhibitory coding sequence for Ser-1200 phosphorylation.
Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in the biogenesis of long chain fatty acids. The phosphorylation of the Ser-1200 residue by cyclic AMP-dependent protein kinase transforms ACC from a citrate-independent form to a citrate-dependent form (10, 16). We have isolated ACC cDNA clones with and without 24 bases which code for 8 additional amino acids located 4 residues upstream to the Ser-1200. The presence of the 8 extra amino acids inhibits the in vitro phosphorylation of the Ser-1200 by the catalytic subunit of cyclic AMP-dependent protein kinase. The S1 nuclease protection experiments indicate that the corresponding two ACC mRNA species occur in vivo. Furthermore, the occurrence of the two forms of ACC mRNA is regulated under different physiological conditions for lipogenesis in a tissue-specific manner. The existence of two forms of ACC mRNA provides the basis for the existence of isozymes of ACC whose Ser-1200 can be selectively phosphorylated. The location of this regulatory sequence for a specific phosphorylation site represents a new regulatory mechanism for protein phosphorylation.
Kong
I S
IS
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.
López-Casillas
F
F
Kim
K H
KH
D000103:Acetyl-CoA Carboxylase / Q000235:genetics* / Q000302:isolation & purification; D000273:Adipose Tissue / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics* / Q000302:isolation & purification; D008025:Ligases / Q000235:genetics*; D008297:Male; D008321:Mammary Glands, Animal / Q000201:enzymology; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D010766:Phosphorylation; D010957:Plasmids; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification; D012694:Serine; D014158:Transcription, Genetic
D003062:Codon; D004041:Dietary Fats; D007527:Isoenzymes; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012694:Serine; D004247:DNA; D011494:Protein Kinases; D008025:Ligases; D000103:Acetyl-CoA Carboxylase