Modification of glycogen synthase activity in isolated rat hepatocytes by tumor-promoting phorbol esters: Evidence for differential regulation of glycogen synthase and phosphorylase

Peter Roach, M. Goldman

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Abstract

Glycogen synthase (UDPglucose:glycogen 4-α-D-glucosyltransferase, EC 2.4.1.11), in isolated rat hepatocytes, has been identified as a novel intracellular target for tumor-promoting phorbol esters such as phorbol 12-tetradecanoate 13-acetate (TPA). Exposure of hepatocytes to TPA resulted in a 50% decrease in the activity ratio of glycogen synthase without/with glucose 6-phosphate. The inactivation was dose dependent and was half-maximal at a TPA concentration of approximately 16 nM (10 ng/ml). Phorbol and phorbol 13-monoacetate, ineffective tumor promoters, had little influence on glycogen synthase activity. Other biologically active diesters, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate, and phorbol 12,13-dibenzoate, caused significant inactivation of glycogen synthase. Glycogen phosphorylase (1,4-α-D-glucan:orthophosphate α-D-glucosyltransferase, EC 2.4.1.1) activity, however, was unaffected by TPA or any of the tumor-promoting phorbol esters mentioned above. It is concluded that phorbol diesters can interact in the regulatory pathway for glycogen synthase, but the lack of effect on phosphorylase argues that distinct mechanisms can operate for the control of glycogen synthase and phosphorylase.

Original languageEnglish
Pages (from-to)7170-7172
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number23 I
StatePublished - 1983

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Glycogen Phosphorylase
Glycogen Synthase
Phorbol Esters
Hepatocytes
Neoplasms
Myristates
Phorbol 12,13-Dibutyrate
Phosphorylases
Glucose-6-Phosphate
Glycogen
Carcinogens
Acetates
Phosphates

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Modification of glycogen synthase activity in isolated rat hepatocytes by tumor-promoting phorbol esters: Evidence for differential regulation of glycogen synthase and phosphorylase",
abstract = "Glycogen synthase (UDPglucose:glycogen 4-α-D-glucosyltransferase, EC 2.4.1.11), in isolated rat hepatocytes, has been identified as a novel intracellular target for tumor-promoting phorbol esters such as phorbol 12-tetradecanoate 13-acetate (TPA). Exposure of hepatocytes to TPA resulted in a 50{\%} decrease in the activity ratio of glycogen synthase without/with glucose 6-phosphate. The inactivation was dose dependent and was half-maximal at a TPA concentration of approximately 16 nM (10 ng/ml). Phorbol and phorbol 13-monoacetate, ineffective tumor promoters, had little influence on glycogen synthase activity. Other biologically active diesters, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate, and phorbol 12,13-dibenzoate, caused significant inactivation of glycogen synthase. Glycogen phosphorylase (1,4-α-D-glucan:orthophosphate α-D-glucosyltransferase, EC 2.4.1.1) activity, however, was unaffected by TPA or any of the tumor-promoting phorbol esters mentioned above. It is concluded that phorbol diesters can interact in the regulatory pathway for glycogen synthase, but the lack of effect on phosphorylase argues that distinct mechanisms can operate for the control of glycogen synthase and phosphorylase.",
author = "Peter Roach and M. Goldman",
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TY - JOUR

T1 - Modification of glycogen synthase activity in isolated rat hepatocytes by tumor-promoting phorbol esters

T2 - Evidence for differential regulation of glycogen synthase and phosphorylase

AU - Roach, Peter

AU - Goldman, M.

PY - 1983

Y1 - 1983

N2 - Glycogen synthase (UDPglucose:glycogen 4-α-D-glucosyltransferase, EC 2.4.1.11), in isolated rat hepatocytes, has been identified as a novel intracellular target for tumor-promoting phorbol esters such as phorbol 12-tetradecanoate 13-acetate (TPA). Exposure of hepatocytes to TPA resulted in a 50% decrease in the activity ratio of glycogen synthase without/with glucose 6-phosphate. The inactivation was dose dependent and was half-maximal at a TPA concentration of approximately 16 nM (10 ng/ml). Phorbol and phorbol 13-monoacetate, ineffective tumor promoters, had little influence on glycogen synthase activity. Other biologically active diesters, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate, and phorbol 12,13-dibenzoate, caused significant inactivation of glycogen synthase. Glycogen phosphorylase (1,4-α-D-glucan:orthophosphate α-D-glucosyltransferase, EC 2.4.1.1) activity, however, was unaffected by TPA or any of the tumor-promoting phorbol esters mentioned above. It is concluded that phorbol diesters can interact in the regulatory pathway for glycogen synthase, but the lack of effect on phosphorylase argues that distinct mechanisms can operate for the control of glycogen synthase and phosphorylase.

AB - Glycogen synthase (UDPglucose:glycogen 4-α-D-glucosyltransferase, EC 2.4.1.11), in isolated rat hepatocytes, has been identified as a novel intracellular target for tumor-promoting phorbol esters such as phorbol 12-tetradecanoate 13-acetate (TPA). Exposure of hepatocytes to TPA resulted in a 50% decrease in the activity ratio of glycogen synthase without/with glucose 6-phosphate. The inactivation was dose dependent and was half-maximal at a TPA concentration of approximately 16 nM (10 ng/ml). Phorbol and phorbol 13-monoacetate, ineffective tumor promoters, had little influence on glycogen synthase activity. Other biologically active diesters, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate, and phorbol 12,13-dibenzoate, caused significant inactivation of glycogen synthase. Glycogen phosphorylase (1,4-α-D-glucan:orthophosphate α-D-glucosyltransferase, EC 2.4.1.1) activity, however, was unaffected by TPA or any of the tumor-promoting phorbol esters mentioned above. It is concluded that phorbol diesters can interact in the regulatory pathway for glycogen synthase, but the lack of effect on phosphorylase argues that distinct mechanisms can operate for the control of glycogen synthase and phosphorylase.

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