Transcriptional activation of the rat liver tyrosine aminotransferase gene by cAMP

Abstract

The enzyme tyrosine aminotransferase (Tyr-ATase; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), which is synthesized in rat liver, is induced by glucocorticoids, insulin, and glucagon or its intracellular mediator cAMP. We have used cloned TyrATase genomic and cDNA sequences to study the mechanism of induction by cAMP. RNA blot analysis shows that cAMP causes a rapid 5-fold increase in TyrATase mRNA concentration in rat liver. Transcription in isolated rat liver nuclei was studied to determine the relative rate of transcription of the TyrATase gene after cAMP administration. We show that the accumulation of TyrATase mRNA after cAMP stimulation is a consequence of transcriptional activation of the TyrATase gene. Combined dexamethasone and cAMP treatment leads to higher TyrATase mRNA concentrations than each inducer alone, which implies that dexamethasone and cAMP act by distinct mechanisms.