The RIIbeta regulatory subunit of protein kinase A binds to cAMP response element: an alternative cAMP signaling pathway.
cAMP, through the activation of cAMP-dependent protein kinase (PKA), is involved in transcriptional regulation. In eukaryotic cells, cAMP is not considered to alter the binding affinity of CREB/ATF to cAMP-responsive element (CRE) but to induce serine phosphorylation and consequent increase in transcriptional activity. In contrast, in prokaryotic cells, cAMP enhances the DNA binding of the catabolite repressor protein to regulate the transcription of several operons. The structural similarity of the cAMP binding sites in catabolite repressor protein and regulatory subunit of PKA type II (RII) suggested the possibility of a similar role for RII in eukaryotic gene regulation. Herein we report that RIIbeta subunit of PKA is a transcription factor capable of interacting physically and functionally with a CRE. In contrast to CREB/ATF, the binding of RIIbeta to a CRE was enhanced by cAMP, and in addition, RIIbeta exhibited transcriptional activity as a Gal4-RIIbeta fusion protein. These experiments identify RIIbeta as a component of an alternative pathway for regulation of CRE-directed transcription in eukaryotic cells.
Srivastava
R K
RK
Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Building 10, Room 5B05, Bethesda, MD 20892-1750, USA.
Lee
Y N
YN
Noguchi
K
K
Park
Y G
YG
Ellis
M J
MJ
Jeong
J S
JS
Kim
S N
SN
Cho-Chung
Y S
YS
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism*; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C517838:Prkar2b protein, mouse; D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases