(Circulation. 1995;92:2041-2043.)
© 1995 American Heart Association, Inc.
Articles |
cAMP Response Element Binding Protein Is Expressed and Phosphorylated in the Human Heart
From the Institut für Pharmakologie und Toxikologie (F.U.M., P.B., A.H., J.K., B.L., W.S., U.V.) and the Klinik und Poliklinik für Thorax-, Herz-, und Gefäßchirurgie (M.C.D., H.H.S.), Universität Münster (Germany) and the Medizinische Klinik III, Universität Köln (Germany).
Correspondence to Dr Frank Ulrich Müller, Institut für Pharmakologie und Toxikologie, Universität Münster, Domagkstraße 12, D-48129 Münster, Germany. E-mail mullerf@uni-muenster.de.
Background In end-stage failing human hearts and in rat hearts after prolonged in vivo ß-adrenergic treatment, several proteins involved in the cAMP-dependent signal transduction are altered on the protein, mRNA, or transcriptional level, eg, ß-adrenoceptors, G-proteins, or proteins of Ca2+ homeostasis. In many tissues, cAMP-dependent transcriptional regulation occurs through the cAMP response element binding protein (CREB) and related transcription factors binding as dimers to cAMP response elements (CREs) in the promoter regions of regulated genes.
Methods and Results To investigate a possible role of CREB in the human heart, nuclear protein of explanted failing and nonfailing human hearts was used to test for CRE specific binding properties in gel mobility shift assays. CRE specific binding was found in competition studies, and CREB and its phosphorylated form were immunologically identified in supershift experiments. The alternatively spliced CREB isoforms CREB327 and CREB341 were found to be expressed on the mRNA level by the reverse transcriptase–polymerase chain reaction.
Conclusions We conclude that in the failing and nonfailing human heart, CREB is expressed on the protein and mRNA levels and that CREB is phosphorylated and able to bind to CREs, indicating a functional role of CREB in the human heart.
Key Words: cardiomyopathy • molecular biology • signal transduction
This article has been cited by other articles:
 |
|
 |
|
  G. S. Huggins, J. J. Lepore, S. Greytak, R. Patten, R. McNamee, M. Aronovitz, P. J. Wang, and G. L. Reed The CREB leucine zipper regulates CREB phosphorylation, cardiomyopathy, and lethality in a transgenic model of heart failure Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1877 - H1882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Matus, G. Lewin, F. Stumpel, I. B. Buchwalow, M. D. Schneider, G. Schutz, W. Schmitz, and F. U. Muller Cardiomyocyte-specific inactivation of transcription factor CREB in mice FASEB J, June 1, 2007; 21(8): 1884 - 1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. U. Muller, G. Lewin, H. A. Baba, P. Boknik, L. Fabritz, U. Kirchhefer, P. Kirchhof, K. Loser, M. Matus, J. Neumann, et al. Heart-directed Expression of a Human Cardiac Isoform of cAMP-Response Element Modulator in Transgenic Mice J. Biol. Chem., February 25, 2005; 280(8): 6906 - 6914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. ISODA, N. PAOLOCCI, K. HAGHIGHI, C. WANG, Y. WANG, D. GEORGAKOPOULOS, G. SERVILLO, M. A. DELLA FAZIA, E. G. KRANIAS, A. A. DEPAOLI-ROACH, et al. Novel regulation of cardiac force-frequency relation by CREM (cAMP response element modulator) FASEB J, February 1, 2003; 17(2): 144 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. B. Mehrhof, F. U. Muller, M. W. Bergmann, P. Li, Y. Wang, W. Schmitz, R. Dietz, and R. von Harsdorf In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated Protein Kinase-Dependent Activation of the Transcription Factor cAMP Response Element-Binding Protein Circulation, October 23, 2001; 104(17): 2088 - 2094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Lakshminarayanan, M. Lewallen, N. G. Frangogiannis, A. J. Evans, K. E. Wedin, L. H. Michael, and M. L. Entman Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia Am. J. Pathol., October 1, 2001; 159(4): 1301 - 1311. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. U Muller, P. Boknik, J. Knapp, B. Linck, H. Luss, J. Neumann, and W. Schmitz Activation and inactivation of cAMP-response element-mediated gene transcription in cardiac myocytes Cardiovasc Res, October 1, 2001; 52(1): 95 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Williams and D. A. Ford Calcium-independent phospholipase A2 mediates CREB phosphorylation and c-fos expression during ischemia Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H168 - H176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar, D. H. Mitchell, J. T. Colston, and G. L. Freeman Regulation of CCAAT/Enhancer Binding Protein, Interleukin-6, Interleukin-6 Receptor, and gp130 Expression During Myocardial Ischemia/Reperfusion Circulation, January 26, 1999; 99(3): 427 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. U. Müller, P. Bokník, J. Knapp, J. Neumann, U. Vahlensieck, E. Oetjen, H. H. Scheld, and W. Schmitz Identification and expression of a novel isoform of cAMP response element modulator in the human heart FASEB J, September 1, 1998; 12(12): 1191 - 1199. [Abstract] [Full Text]
|
|
|
|
|
|
S. T Rapundalo Cardiac protein phosphorylation: functional and pathophysiological correlates Cardiovasc Res, June 1, 1998; 38(3): 559 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cornelius, S. R. Holmer, F. U. Muller, G. A. J. Riegger, and H. Schunkert Regulation of the Rat Atrial Natriuretic Peptide Gene After Acute Imposition of Left Ventricular Pressure Overload Hypertension, December 1, 1997; 30(6): 1348 - 1355. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Luo, A. Chaudhuri, K. R. Johnson, K. Neote, V. Zbrzezna, Y. He, and A. O. Pogo Cloning, Characterization, and Mapping of a Murine Promiscuous Chemokine Receptor Gene: Homolog of the Human Duffy Gene Genome Res., September 1, 1997; 7(9): 932 - 941. [Abstract] [Full Text] [PDF]
|
|