GSK-3β regulation in skeletal muscles by adrenaline and insulin: Evidence that PKA and PKB regulate different pools of GSK-3

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • Natl. Inst. of Occupational Health
  • University of Auckland

Abstract

We have recently shown that while adrenaline alone has no effect on the activation of Protein Kinase B (PKB) in rat soleus muscle, it greatly potentiates the effects of insulin (Brennesvik et al., Cellular Signalling 17: 1551-1559, 2005). In the current study we went on to investigate whether this was paralleled by a similar effect on GSK-3, which is a major PKB target. Surprisingly adrenaline alone increased phosphorylation of GSK-3β Ser9 and GSK-3α Ser21 and adrenaline's effects were additive with those of insulin but did not synergistically potentiate insulin action. Dibutyryl-cAMP (5 mM) and the PKA specific cAMP analogue N6-Benzoyl-cAMP (2 mM) increased GSK-3β Ser9 phosphorylation, whereas the Epac specific cAMP analogue 8-(4-chlorophenylthio)-2′-O-methyl-cAMP (1 mM) did not. Wortmannin (PI 3-kinase inhibitor; 1 μM) blocked insulin-stimulated GSK-3 phosphorylation completely, but adrenaline increased GSK-3β Ser9 phosphorylation in the presence of wortmannin. The PKA inhibitor H89 (50 μM) reduced adrenaline-stimulated GSK-3β Ser9 phosphorylation but did not influence the effects of insulin. Insulin-stimulated GSK-3 Ser9 phosphorylation was paralleled by decreased glycogen synthase phosphorylation at the sites phosphorylated by GSK-3 as expected. However, adrenaline-stimulated GSK-3 Ser9 phosphorylation was paralleled by increased glycogen synthase phosphorylation indicating this pool of GSK-3 may not be directly involved in phosphorylation of glycogen synthase. Our results indicate the existence of at least two distinct pools of GSK-3β in soleus muscle, one phosphorylated by PKA and another by PKB. Further, we hypothesise that each of these pools is involved in the control of different cellular processes.

Details

Original languageEnglish
Pages (from-to)204-210
Number of pages7
JournalCellular Signalling
Volume19
Issue number1
Early online date24 Aug 2006
Publication statusPublished - 1 Jan 2007

Keywords

  • 8-pCPT-2′-O-Me-cAMP, AKAP, Akt, cAMP, Glycogen synthase kinase, GSK3

ASJC Scopus subject areas