Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1

Susana Alemany; Philip Cohen

doi:10.1016/0014-5793(86)80404-5

Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1

Susana Alemany, Philip Cohen

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75 Citations (Scopus)

Abstract

The dephosphorylation of glycogen synthase by protein phosphatase-1 in hepatic glycogen and microsomes was inhibited by nanomolar concentrations of phosphorylase a. The I₅₀ for phosphorylase a was 1000-fold lower than its K_m as a substrate, while tryptic digestion increased the I₅₀ 1000-fold without affecting K_m. Protein phosphatase-1 from skeletal muscle and protein phosphatase-2A from liver were only inhibited at 1000-fold higher concentrations. Protein phosphatase-1 became desensitized to phosphorylase a when released from hepatic microsomes, but sensititvity was partially restored by readdition of the solubilized enzyme to the microsomes. The results demonstrate that phosphorylase a is a potent allosteric inhibitor of hepatic protein phosphatase-1 and suggest that inhibition may be conferred by a novel phosphorylase a-binding subunit.

Original language	English
Pages (from-to)	194-202
Number of pages	9
Journal	FEBS Letters
Volume	198
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(86)80404-5
Publication status	Published - 31 Mar 1986

Keywords

(Liver)
Glycogen synthase
Hormonal regulation
Microsome
Protein phosphatase-1
Protein phosphorylation

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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title = "Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1",

abstract = "The dephosphorylation of glycogen synthase by protein phosphatase-1 in hepatic glycogen and microsomes was inhibited by nanomolar concentrations of phosphorylase a. The I50 for phosphorylase a was 1000-fold lower than its Km as a substrate, while tryptic digestion increased the I50 1000-fold without affecting Km. Protein phosphatase-1 from skeletal muscle and protein phosphatase-2A from liver were only inhibited at 1000-fold higher concentrations. Protein phosphatase-1 became desensitized to phosphorylase a when released from hepatic microsomes, but sensititvity was partially restored by readdition of the solubilized enzyme to the microsomes. The results demonstrate that phosphorylase a is a potent allosteric inhibitor of hepatic protein phosphatase-1 and suggest that inhibition may be conferred by a novel phosphorylase a-binding subunit.",

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author = "Susana Alemany and Philip Cohen",

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T1 - Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1

AU - Alemany, Susana

AU - Cohen, Philip

PY - 1986/3/31

Y1 - 1986/3/31

N2 - The dephosphorylation of glycogen synthase by protein phosphatase-1 in hepatic glycogen and microsomes was inhibited by nanomolar concentrations of phosphorylase a. The I50 for phosphorylase a was 1000-fold lower than its Km as a substrate, while tryptic digestion increased the I50 1000-fold without affecting Km. Protein phosphatase-1 from skeletal muscle and protein phosphatase-2A from liver were only inhibited at 1000-fold higher concentrations. Protein phosphatase-1 became desensitized to phosphorylase a when released from hepatic microsomes, but sensititvity was partially restored by readdition of the solubilized enzyme to the microsomes. The results demonstrate that phosphorylase a is a potent allosteric inhibitor of hepatic protein phosphatase-1 and suggest that inhibition may be conferred by a novel phosphorylase a-binding subunit.

AB - The dephosphorylation of glycogen synthase by protein phosphatase-1 in hepatic glycogen and microsomes was inhibited by nanomolar concentrations of phosphorylase a. The I50 for phosphorylase a was 1000-fold lower than its Km as a substrate, while tryptic digestion increased the I50 1000-fold without affecting Km. Protein phosphatase-1 from skeletal muscle and protein phosphatase-2A from liver were only inhibited at 1000-fold higher concentrations. Protein phosphatase-1 became desensitized to phosphorylase a when released from hepatic microsomes, but sensititvity was partially restored by readdition of the solubilized enzyme to the microsomes. The results demonstrate that phosphorylase a is a potent allosteric inhibitor of hepatic protein phosphatase-1 and suggest that inhibition may be conferred by a novel phosphorylase a-binding subunit.

KW - (Liver)

KW - Glycogen synthase

KW - Hormonal regulation

KW - Microsome

KW - Protein phosphatase-1

KW - Protein phosphorylation

UR - https://www.scopus.com/pages/publications/0022536589

U2 - 10.1016/0014-5793(86)80404-5

DO - 10.1016/0014-5793(86)80404-5

M3 - Article

C2 - 3007211

AN - SCOPUS:0022536589

SN - 0014-5793

VL - 198

SP - 194

EP - 202

JO - FEBS Letters

JF - FEBS Letters

IS - 2

ER -

Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1

Abstract

Keywords

ASJC Scopus subject areas

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