REPRESSION OF C-FOS AND C-JUN GENE-EXPRESSION IS NOT PART OF AT(2) RECEPTOR-COUPLED SIGNAL-TRANSDUCTION

The signal transduction mechanism coupled to angiotensin AT(2) recepto rs is still a matter of debate. Based on the findings that AT(2) recep tor stimulation causes inhibition of proliferation, and that other ant iproliferative agents such as transforming growth factor-beta, retinoi c acid, and MyoD act via repression of immediate early gene (IEG) expr ession, this study was aimed at elucidating whether downregulation of IEG expression is also part of the AT(2) receptor coupled signaling me chanism, Stimulation of angiotensin AT(2) receptors in the rat pheochr omocytoma 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 anti proliferative effect of angiotensin II via the AT(2) receptor is not m ediated by repression of the immediate early genes c-fos and c-jun.