Regulation of the plasma membrane calcium pump gene expression by two signal transduction pathways

The modulation of the plasma membrane calcium pump (PMCA) gene expression is not well understood. We now present evidence that PMCA mRNA is induced by various hormones or agonists via multiple second messenger pathways that include protein kinase C-, cAMP-, and Ca(2+)-dependent mechanisms. Among several types of cultured cells examined, endothelial cells from the rat aorta (RAEC) responded to phorbol ester or angiotensin II with an 8- to 20-fold increase in the PMCA messages, while endothelial cells from the brain resistant vessel (RVEC) exhibited minimal (0- to 2-fold) response to these agonists. On the other hand, under the stimulation of cAMP or thapsigargin (a calcium mobilizing agent), the pattern of response is reversed; only RVEC responded but not RAEC. The results suggest that hormone-induced PMCA gene expression is regulated via two distinct pathways; one involves protein kinase C while the other involves Ca2+ or cAMP. Since the protein kinase A inhibitor (or the calmodulin-dependent kinase inhibitor) was able to block the stimulation elicited by either Ca2+ or cAMP, we suggest that the Ca2+ and cAMP signals share a common passage leading to the induction of PMCA mRNA. The possibility of cross-talk between the distinct second messenger pathways is also discussed.