This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Pilz, R. B. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Pilz, R. B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2003, p. 4066-4082, Vol. 23, No. 12
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.12.4066-4082.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Synergism between Calcium and Cyclic GMP in Cyclic AMP Response Element-Dependent Transcriptional Regulation Requires Cooperation between CREB and C/EBP-ß

Department of Medicine and Cancer Center, University of California at San Diego, La Jolla, California 92093-0652

Received 24 September 2002/ Returned for modification 18 November 2002/ Accepted 18 March 2003

Calcium induces transcriptional activation of the fos promoter by activation of the cyclic AMP response element (CRE)-binding protein (CREB), and in some cells its effect is enhanced synergistically by cyclic GMP (cGMP) through an unknown mechanism. We observed calcium-cGMP synergism in neuronal and osteogenic cells which express type II cGMP-dependent protein kinase (G-kinase); the effect on the fos promoter was mediated by the CRE and proportional to G-kinase activity. Dominant negative transcription factors showed involvement of CREB- and C/EBP-related proteins but not of AP-1. Expression of C/EBP-ß but not C/EBP- or - enhanced the effects of calcium and cGMP on a CRE-dependent reporter gene. The transactivation potential of full-length CREB fused to the DNA-binding domain of Gal4 was increased synergistically by calcium and cGMP, and overexpression of C/EBP-ß enhanced the effect, while a dominant negative C/EBP inhibited it. With a mammalian two-hybrid system, coimmunoprecipitation experiments, and in vitro binding studies, we demonstrated that C/EBP-ß and CREB interacted directly; this interaction involved the C terminus of C/EBP-ß but occurred independently of CREB's leucine zipper domain. CREB Ser¹³³ phosphorylation was stimulated by calcium but not by cGMP; in cGMP-treated cells, ³²PO₄ incorporation into C/EBP-ß was decreased and C/EBP-ß/CRE complexes were increased, suggesting regulation of C/EBP-ß functions by G-kinase-dependent dephosphorylation. C/EBP-ß and CREB associated with the fos promoter in intact cells, and the amount of promoter-associated C/EBP-ß was increased by calcium and cGMP. We conclude that calcium and cGMP transcriptional synergism requires cooperation of CREB and C/EBP-ß, with calcium and cGMP modulating the phosphorylation states of CREB and C/EBP-ß, respectively.

This article has been cited by other articles:

• Cui, T. X., Kwok, R., Schwartz, J. (2008). Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein in GH-stimulated c-fos expression. J Endocrinol 196: 89-100 [Abstract] [Full Text]  
• Zhang, T., Zhuang, S., Casteel, D. E., Looney, D. J., Boss, G. R., Pilz, R. B. (2007). A Cysteine-rich LIM-only Protein Mediates Regulation of Smooth Muscle-specific Gene Expression by cGMP-dependent Protein Kinase. J. Biol. Chem. 282: 33367-33380 [Abstract] [Full Text]  
• Karamanlidis, G., Karamitri, A., Docherty, K., Hazlerigg, D. G., Lomax, M. A. (2007). C/EBPbeta Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression. J. Biol. Chem. 282: 24660-24669 [Abstract] [Full Text]  
• Broderick, K. E., Zhang, T., Rangaswami, H., Zeng, Y., Zhao, X., Boss, G. R., Pilz, R. B. (2007). Guanosine 3',5'-Cyclic Monophosphate (cGMP)/cGMP-Dependent Protein Kinase Induce Interleukin-6 Transcription in Osteoblasts. Mol. Endocrinol. 21: 1148-1162 [Abstract] [Full Text]  
• Moeenrezakhanlou, A., Nandan, D., Shephard, L., Reiner, N. E. (2007). 1{alpha},25-Dihydroxycholecalciferol activates binding of CREB to a CRE site in the CD14 promoter and drives promoter activity in a phosphatidylinositol-3 kinase-dependent manner. J. Leukoc. Biol. 81: 1311-1321 [Abstract] [Full Text]  
• McCauslin, C. S., Heath, V., Colangelo, A. M., Malik, R., Lee, S., Mallei, A., Mocchetti, I., Johnson, P. F. (2006). CAAT/Enhancer-binding Protein {delta} and cAMP-response Element-binding Protein Mediate Inducible Expression of the Nerve Growth Factor Gene in the Central Nervous System. J. Biol. Chem. 281: 17681-17688 [Abstract] [Full Text]  
• Jurado, S., Rodriguez-Pascual, F., Sanchez-Prieto, J., Reimunde, F. M., Lamas, S., Torres, M. (2006). NMDA induces post-transcriptional regulation of {alpha}2-guanylyl-cyclase-subunit expression in cerebellar granule cells. J. Cell Sci. 119: 1622-1631 [Abstract] [Full Text]  
• Zhao, X., Zhuang, S., Chen, Y., Boss, G. R., Pilz, R. B. (2005). Cyclic GMP-dependent Protein Kinase Regulates CCAAT Enhancer-binding Protein {beta} Functions through Inhibition of Glycogen Synthase Kinase-3. J. Biol. Chem. 280: 32683-32692 [Abstract] [Full Text]  
• Broderick, K. E., Singh, V., Zhuang, S., Kambo, A., Chen, J. C., Sharma, V. S., Pilz, R. B., Boss, G. R. (2005). Nitric Oxide Scavenging by the Cobalamin Precursor Cobinamide. J. Biol. Chem. 280: 8678-8685 [Abstract] [Full Text]  
• Peluso, J.J., Pappalardo, A. (2004). Progesterone Regulates Granulosa Cell Viability Through a Protein Kinase G-Dependent Mechanism That May Involve 14-3-3{sigma}. Biol. Reprod. 71: 1870-1878 [Abstract] [Full Text]