Repression of c-fos and c-jun gene expression is not part of AT2 receptor coupled signal transduction

The signal transduction mechanism coupled to angiotensin AT(2) receptors is still a matter of debate. Based on the findings that AT(2) receptor stimulation causes inhibition of proliferation, and that other antiproliferative agents such as transforming growth factor-beta, retinoic acid, and MyoD act via repression of immediate early gene (IEG) expression, this study was aimed at elucidating whether downregulation of IEG expression is also part of the AT(2) receptor coupled signaling mechanism, Stimulation of angiotensin AT(2) receptors in the rat pheochromocytoma cell line PC12 W following pretreatment with growth factors was able to counteract growth factor induced proliferation but not to repress growth factor induced c-fos and c-jun expression; neither did AT(2) receptor stimulation cause an induction of c-fos expression. We conclude that, in contrast to other growth-inhibiting agents, the antiproliferative effect of angiotensin II via the AT(2) receptor is not mediated by repression of the immediate early genes c-fos and c-jun.