Human skeletal muscle expresses a glycogen-targeting subunit of PP1 that is identical to the insulin-sensitive glycogen-targeting subunit G(L) of liver.
Insulin has been previously shown to regulate the expression of the hepatic glycogen-targeting subunit, G(L), of protein phosphatase 1 (PP1) and is believed to control the activity of the PP1-G(L) complex by modulation of the level of phosphorylase a, which allosterically inhibits the activity of PP1-G(L). These mechanisms contribute to the ability of insulin to increase hepatic glycogen synthesis. Human G(L) shows >88% amino acid identity to its rat and mouse homologs, with complete conservation of the phosphorylase a binding site. G(L) is highly expressed in the liver and present at appreciable levels in heart tissue of all three species. Surprisingly, G(L) is highly expressed in human skeletal muscle while only being detected at very low levels in rat, mouse, and rabbit skeletal muscle. The amino acid sequence of G(L) predicted from the cDNA is identical in human liver and skeletal muscle and encoded by a gene on chromosome 8 at p23.1. The species-specific difference in the level of expression of G(L) mRNA and protein in skeletal muscle has important implications for understanding the mechanisms by which insulin regulates glycogen synthesis in human skeletal muscle and for questions regarding whether rodents are appropriate models for this purpose.
Munro
Shonagh
S
Medical Research Council Protein Phosphorylation Unit, School of Life Sciences,University of Dundee, Dundee, Scotland, U.K.
Cuthbertson
Daniel J R
DJ
Cunningham
Joan
J
Sales
Mark
M
Cohen
Patricia T W
PT
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001706:Biopsy; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D004247:DNA / Q000032:analysis / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry; D015870:Gene Expression; D015723:Gene Library; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D054645:Protein Phosphatase 1; D012333:RNA, Messenger; D051381:Rats; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D007328:Insulin; D012333:RNA, Messenger; D006003:Glycogen; D004247:DNA; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1