Human Skeletal Muscle Expresses a Glycogen-Targeting Subunit of PP1 That Is Identical to the Insulin-Sensitive Glycogen-Targeting Subunit GL of Liver
- 1Medical Research Council Protein Phosphorylation Unit, School of Life Sciences,University of Dundee, Dundee, Scotland, U.K.
- 2Clinical Investigation Unit, Ninewells Hospital Medical School, University of Dundee, Dundee, Scotland, U.K.
- 3Department of Human Genetics (Cytogenetics), Ninewells Hospital Medical School, University of Dundee, Dundee, Scotland, U.K.
Insulin has been previously shown to regulate the expression of the hepatic glycogen-targeting subunit, GL, of protein phosphatase 1 (PP1) and is believed to control the activity of the PP1-GL complex by modulation of the level of phosphorylase a, which allosterically inhibits the activity of PP1-GL. These mechanisms contribute to the ability of insulin to increase hepatic glycogen synthesis. Human GL shows >88% amino acid identity to its rat and mouse homologs, with complete conservation of the phosphorylase a binding site. GL is highly expressed in the liver and present at appreciable levels in heart tissue of all three species. Surprisingly, GL 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 GL 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 GL 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.
Address correspondence and reprint requests to Professor P.T.W. Cohen, MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow St., Dundee DD1 5EH, Scotland, U.K. E-mail:.
Received for publication 21 September 2001 and accepted in revised form 26 November 2001.
P.T.W.C. has received research funds from AstraZeneca, Boehringer, Ingelheim, Glaxo SmithKline, Novo Nordisk, and Pfizer.
BAC, Bacterial Artificial Chromosome; GSK3, glycogen synthase kinase-3; HGMP, Human Genome Mapping Project; NCBI, National Center for Biotechnology Information; nt, nucleotide; PKA, protein kinase A; PKB, protein kinase B; PI-3 kinase, phosphatidylinositol-3 kinase; PP1, protein phosphatase 1; PP1c, PP1 catalytic subunit; RACE, rapid amplification of cDNA ends; UTR, untranslated region.