Insulin inhibits dephosphorylation of adenosine 3',5'-monophosphate response element-binding protein/activating transcription factor-1: effect on nuclear phosphoserine phosphatase-2a.
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.
Reusch
J E
JE
Medical Research Service, Veterans Affairs Medical Center, Denver, Colorado.
Hsieh
P
P
Klemm
D
D
Hoeffler
J
J
Draznin
B
B
D051697:Activating Transcription Factor 1; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins; D007328:Insulin / Q000502:physiology*; D010449:Peptide Mapping; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism*
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D007328:Insulin; D014157:Transcription Factors; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase