Identification of the separate domains in the hepatic glycogen-targeting subunit of protein phosphatase 1 that interact with phosphorylase a, glycogen and protein phosphatase 1.
Deletion and mutational analyses of the rat liver glycogen-targeting subunit (GL) of protein phosphatase 1 (PP1) have identified three separate domains that are responsible for binding of PP1, glycogen and phosphorylase a. The glycogen-binding domain spans the centre of GL between residues 144 and 231 and appears to be distinct from the glycogen-binding (storage) site of phosphorylase. The regulatory high-affinity binding site for phosphorylase a lies in the 16 amino acids at the C-terminus of GL. The PP1-binding domain is deduced to comprise the -RVXF- motif [Egloff, Johnson, Moorhead, Cohen and Barford (1997) EMBO J. 16, 1876-1887] located at residues 61-64 of GL and preceding lysine residues at positions 56, 57 and 59. A possible approach for increasing glycogen synthesis in certain disorders is discussed.
Armstrong
C G
CG
Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD15EH, Scotland, U.K. cgarmstrong@bad.dundee.ac.uk
Doherty
M J
MJ
Cohen
P T
PT
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008112:Liver Glycogen / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011487:Protein Conformation; D054645:Protein Phosphatase 1; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae
D002352:Carrier Proteins; D008112:Liver Glycogen; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; D010762:Phosphorylase a; D005982:Glutathione Transferase; D010749:Phosphoprotein Phosphatases; C498442:Ppp1r3b protein, mouse; C114052:Ppp1r3b protein, rat; D054645:Protein Phosphatase 1