INSULIN INHIBITS DEPHOSPHORYLATION OF ADENOSINE-3',5'-MONOPHOSPHATE RESPONSE ELEMENT-BINDING PROTEIN ACTIVATING TRANSCRIPTION FACTOR-I - EFFECT ON NUCLEAR PHOSPHOSERINE PHOSPHATASE-2A

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