Protein kinase A Linked phosphorylation mediates triiodothyronine induced actin gene expression in developing brain

In the developing rat cerebra, triiodothyronine (T-3) stimulates actin mRNA by acting predominantly at the level of transcription whereas tubulin mRNA is enhanced primarily by post-transcriptional regulation. We report here t hat in primary cultures of rat cerebra, the T-3-induced actin gene expressi on is mediated by phosphorylation events. Inhibition of protein kinase A (P KA), but not of protein kinase C (PKC) or tyrosine kinase, totally blocked the induction of actin mRNA by T-3. Under identical conditions, induction o f tubulin mRNA by T-3 was virtually unaffected by all the inhibitors. Activ ators of PKA, but not of PKC, potentiated the T-3-induced actin gene expres sion, both at mRNA and protein level, by about 2-fold. In the absence of T- 3, neither the inhibitor nor the activator of PKA had any significant effec t on this induction. The involvement of PKA in mediating the induction of a ctin mRNA by T-3 was confirmed by transfecting primary cultures of rat cere bra with an expression vector encoding the protein kinase A inhibitor which totally abolished the induction. T-3 is shown to enhance the phosphorylati on of the thyroid hormone receptor, TR alpha, by about 2-fold but the level of phosphorylation of TR beta remained virtually unaffected. (C) 1999 Else vier Science B.V. All rights reserved.