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

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2000, p. 702-712, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Integration of Calcium and Cyclic AMP Signaling Pathways by 14-3-3

Chi-Wing Chow and Roger J. Davis*

Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 21 April 1999/Accepted 13 October 1999

Calcium-stimulated nuclear factor of activated T cells (NFAT) transcription activity at the interleukin-2 promoter is negatively regulated by cyclic AMP (cAMP). This effect of cAMP is mediated, in part, by protein kinase A phosphorylation of NFAT. The mechanism of regulation involves the creation of a phosphorylation-dependent binding site for 14-3-3. Decreased NFAT phosphorylation caused by the calcium-stimulated phosphatase calcineurin, or mutation of the PKA phosphorylation sites, disrupted 14-3-3 binding and increased NFAT transcription activity. In contrast, NFAT phosphorylation caused by cAMP increased 14-3-3 binding and reduced NFAT transcription activity. The regulated interaction between NFAT and 14-3-3 provides a mechanism for the integration of calcium and cAMP signaling pathways.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-6054. Fax: (508) 856-3210. E-mail: Roger.Davis{at}Ummed.Edu.

Molecular and Cellular Biology, January 2000, p. 702-712, Vol. 20, No. 2
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • la Sala, A., He, J., Laricchia-Robbio, L., Gorini, S., Iwasaki, A., Braun, M., Yap, G. S., Sher, A., Ozato, K., Kelsall, B. (2009). Cholera toxin inhibits IL-12 production and CD8{alpha}+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function. JEM 206: 1227-1235 [Abstract] [Full Text]  
  • Mehta, S., Li, H., Hogan, P. G., Cunningham, K. W. (2009). Domain Architecture of the Regulators of Calcineurin (RCANs) and Identification of a Divergent RCAN in Yeast. Mol. Cell. Biol. 29: 2777-2793 [Abstract] [Full Text]  
  • Klein-Hessling, S., Bopp, T., Jha, M. K., Schmidt, A., Miyatake, S., Schmitt, E., Serfling, E. (2008). Cyclic AMP-induced Chromatin Changes Support the NFATc-mediated Recruitment of GATA-3 to the Interleukin 5 Promoter. J. Biol. Chem. 283: 31030-31037 [Abstract] [Full Text]  
  • Kim, S.-Y., Seo, M., Kim, Y., Lee, Y.-I., Oh, J.-M., Cho, E.-A., Kang, J.-S., Juhnn, Y.-S. (2008). Stimulatory Heterotrimeric GTP-binding Protein Inhibits Hydrogen Peroxide-induced Apoptosis by Repressing BAK Induction in SH-SY5Y Human Neuroblastoma Cells. J. Biol. Chem. 283: 1350-1361 [Abstract] [Full Text]  
  • Faul, C., Dhume, A., Schecter, A. D., Mundel, P. (2007). Protein Kinase A, Ca2+/Calmodulin-Dependent Kinase II, and Calcineurin Regulate the Intracellular Trafficking of Myopodin between the Z-Disc and the Nucleus of Cardiac Myocytes. Mol. Cell. Biol. 27: 8215-8227 [Abstract] [Full Text]  
  • Cho, Y.-Y., Yao, K., Bode, A. M., Bergen, H. R. III, Madden, B. J., Oh, S.-M., Ermakova, S., Kang, B. S., Choi, H. S., Shim, J.-H., Dong, Z. (2007). RSK2 Mediates Muscle Cell Differentiation through Regulation of NFAT3. J. Biol. Chem. 282: 8380-8392 [Abstract] [Full Text]  
  • Rong, J., Li, S., Sheng, G., Wu, M., Coblitz, B., Li, M., Fu, H., Li, X.-J. (2007). 14-3-3 Protein Interacts with Huntingtin-associated Protein 1 and Regulates Its Trafficking. J. Biol. Chem. 282: 4748-4756 [Abstract] [Full Text]  
  • Winteringham, L. N., Endersby, R., Kobelke, S., McCulloch, R. K., Williams, J. H., Stillitano, J., Cornwall, S. M., Ingley, E., Klinken, S. P. (2006). Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule. J. Biol. Chem. 281: 38791-38800 [Abstract] [Full Text]  
  • Belfield, J. L., Whittaker, C., Cader, M. Z., Chawla, S. (2006). Differential Effects of Ca2+ and cAMP on Transcription Mediated by MEF2D and cAMP-response Element-binding Protein in Hippocampal Neurons. J. Biol. Chem. 281: 27724-27732 [Abstract] [Full Text]  
  • Nirula, A., Ho, M., Phee, H., Roose, J., Weiss, A. (2006). Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4. JEM 203: 1733-1744 [Abstract] [Full Text]  
  • Hermann-Kleiter, N., Thuille, N., Pfeifhofer, C., Gruber, T., Schafer, M., Zitt, C., Hatzelmann, A., Schudt, C., Leitges, M., Baier, G. (2006). PKC{theta} and PKA are antagonistic partners in the NF-AT transactivation pathway of primary mouse CD3+ T lymphocytes. Blood 107: 4841-4848 [Abstract] [Full Text]  
  • Loza, M. J., Foster, S., Peters, S. P., Penn, R. B. (2006). Beta-agonists modulate T-cell functions via direct actions on type 1 and type 2 cells. Blood 107: 2052-2060 [Abstract] [Full Text]  
  • Hogan, P. G., Chen, L., Nardone, J., Rao, A. (2003). Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17: 2205-2232 [Full Text]  
  • Yang, T. T. C., Chow, C.-W. (2003). Transcription Cooperation by NFAT{middle dot}C/EBP Composite Enhancer Complex. J. Biol. Chem. 278: 15874-15885 [Abstract] [Full Text]  
  • Foucault, I., Liu, Y.-C., Bernard, A., Deckert, M. (2003). The Chaperone Protein 14-3-3 Interacts with 3BP2/SH3BP2 and Regulates Its Adapter Function. J. Biol. Chem. 278: 7146-7153 [Abstract] [Full Text]  
  • Sheridan, C. M., Heist, E. K., Beals, C. R., Crabtree, G. R., Gardner, P. (2002). Protein Kinase A Negatively Modulates the Nuclear Accumulation of NF-ATc1 by Priming for Subsequent Phosphorylation by Glycogen Synthase Kinase-3. J. Biol. Chem. 277: 48664-48676 [Abstract] [Full Text]  
  • Gomez, M. F., Stevenson, A. S., Bonev, A. D., Hill-Eubanks, D. C., Nelson, M. T. (2002). Opposing Actions of Inositol 1,4,5-Trisphosphate and Ryanodine Receptors on Nuclear Factor of Activated T-cells Regulation in Smooth Muscle. J. Biol. Chem. 277: 37756-37764 [Abstract] [Full Text]  
  • Diakos, C., Prieschl, E. E., Saemann, M., Novotny, V., Bohmig, G., Csonga, R., Baumruker, T., Zlabinger, G. J. (2002). Novel Mode of Interference with Nuclear Factor of Activated T-cells Regulation in T-cells by the Bacterial Metabolite n-Butyrate. J. Biol. Chem. 277: 24243-24251 [Abstract] [Full Text]  
  • Yang, T. T. C., Xiong, Q., Enslen, H., Davis, R. J., Chow, C.-W. (2002). Phosphorylation of NFATc4 by p38 Mitogen-Activated Protein Kinases. Mol. Cell. Biol. 22: 3892-3904 [Abstract] [Full Text]  
  • Toshima, J. Y., Toshima, J., Watanabe, T., Mizuno, K. (2001). Binding of 14-3-3beta Regulates the Kinase Activity and Subcellular Localization of Testicular Protein Kinase 1. J. Biol. Chem. 276: 43471-43481 [Abstract] [Full Text]  
  • Yang, T., Davis, R. J., Chow, C.-W. (2001). Requirement of Two NFATc4 Transactivation Domains for CBP Potentiation. J. Biol. Chem. 276: 39569-39576 [Abstract] [Full Text]  
  • Choi, S.-J., Park, S.-Y., Han, T.-H. (2001). 14-3-3{{tau}} associates with and activates the MEF2D transcription factor during muscle cell differentiation. Nucleic Acids Res 29: 2836-2842 [Abstract] [Full Text]  
  • Delgado, M., Ganea, D. (2001). Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Inhibit Expression of Fas Ligand in Activated T Lymphocytes by Regulating c-Myc, NF-{{kappa}}B, NF-AT, and Early Growth Factors 2/3. J. Immunol. 166: 1028-1040 [Abstract] [Full Text]  
  • Chow, C.-W., Dong, C., Flavell, R. A., Davis, R. J. (2000). c-Jun NH2-Terminal Kinase Inhibits Targeting of the Protein Phosphatase Calcineurin to NFATc1. Mol. Cell. Biol. 20: 5227-5234 [Abstract] [Full Text]  
  • Stevenson, A. S., Gomez, M. F., Hill-Eubanks, D. C., Nelson, M. T. (2001). NFAT4 Movement in Native Smooth Muscle. A ROLE FOR DIFFERENTIAL Ca2+ SIGNALING. J. Biol. Chem. 276: 15018-15024 [Abstract] [Full Text]  
  • Conze, D., Krahl, T., Kennedy, N., Weiss, L., Lumsden, J., Hess, P., Flavell, R. A., Le Gros, G., Davis, R. J., Rincon, M. (2002). c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Have Distinct Roles in CD8+ T Cell Activation. JEM 195: 811-823 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»