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 demonstrated directly for the cGMP/cGMP-dependent protein kinase (G-kinase) signal transduction pathway. Here we report that transfection of G-kinase into G-kinase-deficient cells causes activation of the human c-fos promoter in a strictly cGMP-dependent manner. The effect of G-kinase appeared to be mediated by several sequence elements, most notably the 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 significant differences between G-kinase and A-kinase activation of single 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.
Gudi
T
T
Department of Medicine and the Cancer Center, University of California at San Diego, La Jolla, 92093-0652, USA.
Huvar
I
I
Meinecke
M
M
Lohmann
S M
SM
Boss
G R
GR
Pilz
R B
RB
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D016762:Genes, fos; D006801:Humans; D007668:Kidney; D007700:Kinetics; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP