REGULATION OF GENE-EXPRESSION BY CGMP-DEPENDENT PROTEIN-KINASE - TRANSACTIVATION OF THE C-FOS PROMOTER

The cAMP/cAMP-dependent protein kinase (A-kinase) and Ca2+/calmodulin- dependent protein kinase (Cam-kinase) signal transduction pathways are well known to regulate gene transcription, but this has not been demo nstrated directly for the cGMP/cGMP-dependent protein kinase (G-kinase ) signal transduction pathway. Here we report that transfection of G-k inase into G-kinase-deficient cells causes activation of the human c-f os promoter in a strictly cGMP-dependent manner. The effect of G-kinas e appeared to be mediated by several sequence elements, most notably t he serum response element (SRE), the AP-1 binding site (FAP), and the cAMP response element (CRE), The magnitude of G-kinase transactivation of the fos promoter was similar to that of A-kinase, but there were s ignificant differences between G-kinase and A-kinase activation of sin gle enhancer elements and of a chimeric Gal4-CREB transcription factor , Our results indicate that G-kinase transduces signals to the nucleus independently of A-kinase or Ca2+, although it may target some of the same transcription factors as A-kinase and Cam-kinase.