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

Abstract

In the developing rat cerebra, triiodothyronine (T₃) stimulates actin mRNA by acting predominantly at the level of transcription whereas tubulin mRNA is enhanced primarily by post-transcriptional regulation. We report here that in primary cultures of rat cerebra, the T₃-induced actin gene expression is mediated by phosphorylation events. Inhibition of protein kinase A (PKA), but not of protein kinase C (PKC) or tyrosine kinase, totally blocked the induction of actin mRNA by T₃. Under identical conditions, induction of tubulin mRNA by T₃ was virtually unaffected by all the inhibitors. Activators of PKA, but not of PKC, potentiated the T₃-induced actin gene expression, both at mRNA and protein level, by about 2-fold. In the absence of T₃, neither the inhibitor nor the activator of PKA had any significant effect on this induction. The involvement of PKA in mediating the induction of actin mRNA by T₃ was confirmed by transfecting primary cultures of rat cerebra with an expression vector encoding the protein kinase A inhibitor which totally abolished the induction. T₃ is shown to enhance the phosphorylation of the thyroid hormone receptor, TRα , by about 2-fold but the level of phosphorylation of TRβ remained virtually unaffected.