Insulin inhibits dephosphorylation of adenosine 3',5'-monophosphate response element-binding protein/activating transcription factor-1: effect on nuclear phosphoserine phosphatase-2a

Endocrinology. 1994 Dec;135(6):2418-22. doi: 10.1210/endo.135.6.7988426.


We examined the effects of insulin on the phosphorylation state of cAMP response element-binding protein (CREB) in normal rat adipocytes. Insulin increased in vivo phosphorylation of CREB by 40%. Although both phosphoprotein phosphatase-1 and -2A dephosphorylate CREB and activating transcription factor-1, insulin action appears to be mediated via its strong inhibitory effect on nuclear phosphatase-2A (PP-2A) activity. Using in vitro protein kinase-A-phosphorylated activating transcription factor-1 as a substrate, we found that insulin inhibited nuclear PP-2A activity by 80% (P < 0.001), which represents approximately 50% of the total nuclear phosphatase activity. Greater than 50% of the effect of insulin was observed at 0.3 nM and 2 min of exposure. These findings are the first indicator that a signal initiated by a cell surface tyrosine kinase receptor may regulate nuclear PP-2A activity and thereby affect the phosphorylation state of transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Activating Transcription Factor 1
  • Adipocytes / metabolism
  • Animals
  • Cell Nucleus / enzymology*
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Insulin / physiology*
  • Peptide Mapping
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / metabolism*


  • Activating Transcription Factor 1
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Insulin
  • Transcription Factors
  • Phosphoric Monoester Hydrolases
  • phosphoserine phosphatase