The hepatic PP1 glycogen-targeting subunit interaction with phosphorylase a can be blocked by C-terminal tyrosine deletion or an indole drug

Ian R. Kelsall, Shonagh Munro, Irene Hallyburton, Judith L. Treadway, Patricia T. W. Cohen

    Research output: Contribution to journalArticlepeer-review

    28 Citations (Scopus)

    Abstract

    The inhibition of hepatic glycogen-associated protein phosphatase-1 (PP1-G(L)) by glycogen phosphorylase a prevents the dephosphorylation and activation of glycogen synthase, suppressing glycogen synthesis when glycogenolysis is activated. Here, we show that a peptide ((280)LGPYY(284)) comprising the last five amino acids of G(L) retains high-affinity interaction with phosphorylase a and that the two tyrosines play crucial roles. Tyr284 deletion abolishes binding of phosphorylase a to G(L) and replacement by phenylalanine is insufficient to restore high-affinity binding. We show that a phosphorylase inhibitor blocks the interaction of phosphorylase a with the G(L) C-terminus, suggesting that the latter interaction could be targeted to develop an anti-diabetic drug.
    Original languageEnglish
    Pages (from-to)4749-4753
    Number of pages5
    JournalFEBS Letters
    Volume581
    Issue number24
    DOIs
    Publication statusPublished - 2007

    Keywords

    • Amino Acid Sequence
    • Animals
    • Calorimetry
    • Glycogen Phosphorylase, Liver Form
    • Humans
    • Indoles
    • Mice
    • Molecular Sequence Data
    • Mutation
    • Phenylbutyrates
    • Protein Binding
    • Protein Subunits
    • Rabbits
    • Rats
    • Thermodynamics
    • Titrimetry
    • Tyrosine

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