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Science 7 June 1991:
Vol. 252. no. 5011, pp. 1427 - 1430
DOI: 10.1126/science.1646483

Articles

Science, Vol 252, Issue 5011, 1427-1430
Copyright © 1991 by American Association for the Advancement of Science


articles

CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases

M Sheng, MA Thompson, and ME Greenberg

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.

The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca(2+)-regulated transcription factor and as a substrate for depolarization-activated Ca(2+)-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.


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Physiol Rev 81, 1197-1267
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Calcium-independent phospholipase A2 mediates CREB phosphorylation and c-fos expression during ischemia.
S. D. Williams and D. A. Ford (2001)
Am J Physiol Heart Circ Physiol 281, H168-H176
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Developmental Regulation of Mitogen-Activated Protein Kinase-Activated Kinases-2 and -3 (MAPKAPK-2/-3) in Vivo during Corpus Luteum Formation in the Rat.
E. T. Maizels, A. Mukherjee, G. Sithanandam, C. A. Peters, J. Cottom, K. E. Mayo, and M. Hunzicker-Dunn (2001)
Mol. Endocrinol. 15, 716-733
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Protein Kinase C-{{theta}} Participates in the Activation of Cyclic AMP-Responsive Element-Binding Protein and Its Subsequent Binding to the -180 Site of the IL-2 Promoter in Normal Human T Lymphocytes.
E. E. Solomou, Y.-T. Juang, and G. C. Tsokos (2001)
J. Immunol. 166, 5665-5674
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Involvement of PKA, PKC, and Ca2+ in LPS-activated expression of the chicken lysozyme gene.
P. Regenhard, R. Goethe, and L. Phi-van (2001)
J. Leukoc. Biol. 69, 651-658
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Gene Expression Profiling of Rat Brain Neurons Reveals Angiotensin II-Induced Regulation of Calmodulin and Synapsin I: Possible Role in Neuromodulation.
S. Gallinat, S. Busche, H. Yang, M. K. Raizada, and C. Sumners (2001)
Endocrinology 142, 1009-1016
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HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway.
G. ZAULI, D. MILANI, P. MIRANDOLA, M. MAZZONI, P. SECCHIERO, S. MISCIA, and S. CAPITANI (2001)
FASEB J 15, 483-491
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Magnitude of the CREB-Dependent Transcriptional Response Is Determined by the Strength of the Interaction between the Kinase-Inducible Domain of CREB and the KIX Domain of CREB-Binding Protein.
A. J. Shaywitz, S. L. Dove, J. M. Kornhauser, A. Hochschild, and M. E. Greenberg (2000)
Mol. Cell. Biol. 20, 9409-9422
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Cellular Responses to Mechanical Stress: Selected Contribution: Regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells.
M. A. Peake, L. M. Cooling, J. L. Magnay, P. B. M. Thomas, and A. J. El Haj (2000)
J Appl Physiol 89, 2498-2507
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A Family of LIM-Only Transcriptional Coactivators: Tissue-Specific Expression and Selective Activation of CREB and CREM.
G. M. Fimia, D. De Cesare, and P. Sassone-Corsi (2000)
Mol. Cell. Biol. 20, 8613-8622
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Identification and characterization of CKLiK, a novel granulocyte Ca++/calmodulin-dependent kinase.
S. Verploegen, J.-W. J. Lammers, L. Koenderman, and P. J. Coffer (2000)
Blood 96, 3215-3223
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Development of a Facile Method for High Throughput Screening with Reporter Gene Assays.
A. S. Goetz, J. L. Andrews, T. R. Littleton, and D. M. Ignar (2000)
J Biomol Screen 5, 377-384
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Differential Regulation of Mitogen-Activated Protein Kinase-Responsive Genes by the Duration of a Calcium Signal.
P. L. Durham and A. F. Russo (2000)
Mol. Endocrinol. 14, 1570-1582
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The Decorin High Glucose Response Element and Mechanism of Its Activation in Human Mesangial Cells.
N. A. WAHAB, S. PARKER, J.-D. SRAER, and R. M. MASON (2000)
J. Am. Soc. Nephrol. 11, 1607-1619
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Defective Th Function Induced by a Dominant-Negative cAMP Response Element Binding Protein Mutation Is Reversed by Bcl-2.
F. Zhang, M. Rincon, R. A. Flavell, and T. M. Aune (2000)
J. Immunol. 165, 1762-1770
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Chronic Elevation of Calmodulin in the Ventricles of Transgenic Mice Increases the Autonomous Activity of Calmodulin-Dependent Protein Kinase II, Which Regulates Atrial Natriuretic Factor Gene Expression.
J. M. Colomer and A. R. Means (2000)
Mol. Endocrinol. 14, 1125-1136
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Regional Distribution of Protein Kinases in Normal and Odor-deprived Mouse Olfactory Bulbs.
N. Liu (2000)
Chem Senses 25, 401-406
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Differential Modulation of Catecholamines by Chlorotriazine Herbicides in Pheochromocytoma (PC12) Cells in Vitro.
P. C. Das, W. K. McElroy, and R. L. Cooper (2000)
Toxicol. Sci. 56, 324-331
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Induction of cAMP Response Element Modulator (CREM) and Inducible cAMP Early Repressor (ICER) Expression in Rat Brain by Uncompetitive N-Methyl-D-aspartate Receptor Antagonists.
M. Storvik, A.-M. Lindén, O. Kontkanen, M. Lakso, E. Castrén, and G. Wong (2000)
J. Pharmacol. Exp. Ther. 294, 52-60
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