This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durham, P. L. Articles by Russo, A. F. Search for Related Content PubMed PubMed Citation Articles by Durham, P. L. Articles by Russo, A. F.

Differential Regulation of Mitogen-Activated Protein Kinase-Responsive Genes by the Duration of a Calcium Signal

Department of Physiology and Biophysics University of Iowa Iowa City, Iowa 52242

We have investigated the cellular mechanisms by which changes in intracellular calcium (Ca²⁺) can differentially regulate gene expression. Two Ca²⁺ paradigms, involving prolonged and transient Ca²⁺ increases, were used. As a starting point, we studied the slow, prolonged elevation of Ca²⁺ caused by activation of 5-HT₁ receptors. We had previously shown that 5-HT₁ agonists inhibit calcitonin gene-related peptide (CGRP) transcription and secretion. The Ca²⁺ ionophore, ionomycin, was used to produce a prolonged elevation of the Ca²⁺ signal similar to that generated by 5-HT₁ receptor agonists. Ionomycin treatment of the neuronal-like CA77 cell line specifically inhibited mitogen-activated protein (MAP) kinase stimulation of the CGRP enhancer and two synthetic MAP kinase-responsive reporter genes (4- to 10-fold). We then showed that ionomycin repression of promoter activity involved selective induction of MAP kinase phosphatase-1 (MKP-1), but not MKP-2, and that overexpression of MKP-1 was sufficient to repress CGRP enhancer activity. These effects were then compared with a Ca²⁺ paradigm involving a transient elevation in Ca²⁺ as seen after depolarization. At 4 h after the transient increase in Ca²⁺, the CGRP enhancer and synthetic MAP kinase-responsive reporter genes were stimulated. In contrast, exposure to depolarizing stimuli overnight caused only a less than 2-fold inhibition of promoter activity. We propose that the duration of the Ca²⁺ signal can determine the magnitude of a negative feedback loop that leads to differential regulation of MAP kinase-responsive genes.

This article has been cited by other articles:

				T. Boutros, E. Chevet, and P. Metrakos Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer Pharmacol. Rev., September 1, 2008; 60(3): 261 - 310. [Abstract] [Full Text] [PDF]

				K. Horsch, H. de Wet, M. M. Schuurmans, F. Allie-Reid, A. C. B. Cato, J. Cunningham, J. M. Burrin, F. S. Hough, and P. A. Hulley Mitogen-Activated Protein Kinase Phosphatase 1/Dual Specificity Phosphatase 1 Mediates Glucocorticoid Inhibition of Osteoblast Proliferation Mol. Endocrinol., December 1, 2007; 21(12): 2929 - 2940. [Abstract] [Full Text] [PDF]

				J. D. Meissner, K.-C. Chang, H.-P. Kubis, A. R. Nebreda, G. Gros, and R. J. Scheibe The p38{alpha}/beta Mitogen-activated Protein Kinases Mediate Recruitment of CREB-binding Protein to Preserve Fast Myosin Heavy Chain IId/x Gene Activity in Myotubes J. Biol. Chem., March 9, 2007; 282(10): 7265 - 7275. [Abstract] [Full Text] [PDF]

				L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]

				T. J. Viney, T. W. Schmidt, W. Gierasch, A. W. Sattar, R. E. Yaggie, A. Kuburas, J. P. Quinn, J. M. Coulson, and A. F. Russo Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein J. Biol. Chem., November 26, 2004; 279(48): 49948 - 49955. [Abstract] [Full Text] [PDF]

				P. L. Durham and A. F. Russo Stimulation of the Calcitonin Gene-Related Peptide Enhancer by Mitogen-Activated Protein Kinases and Repression by an Antimigraine Drug in Trigeminal Ganglia Neurons J. Neurosci., February 1, 2003; 23(3): 807 - 815. [Abstract] [Full Text] [PDF]

				C. A. Heinlein and C. Chang The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions Mol. Endocrinol., October 1, 2002; 16(10): 2181 - 2187. [Abstract] [Full Text] [PDF]

				K. A. Seta, Z. Spicer, Y. Yuan, G. Lu, and D. E. Millhorn Responding to Hypoxia: Lessons From a Model Cell Line Sci. Signal., August 20, 2002; 2002(146): re11 - re11. [Abstract] [Full Text] [PDF]

				J. Li, M. Puceat, C. Perez-Terzic, A. Mery, K. Nakamura, M. Michalak, K.-H. Krause, and M. E. Jaconi Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis J. Cell Biol., July 8, 2002; 158(1): 103 - 113. [Abstract] [Full Text] [PDF]

				J. E. Dumont, S. Dremier, I. Pirson, and C. Maenhaut Cross signaling, cell specificity, and physiology Am J Physiol Cell Physiol, July 1, 2002; 283(1): C2 - C28. [Abstract] [Full Text] [PDF]

				E. Le Ferrec, D. Lagadic-Gossmann, C. Rauch, C. Bardiau, K. Maheo, F. Massiere, M. Le Vee, A. Guillouzo, and F. Morel Transcriptional Induction of CYP1A1 by Oltipraz in Human Caco-2 Cells Is Aryl Hydrocarbon Receptor- and Calcium-dependent J. Biol. Chem., June 28, 2002; 277(27): 24780 - 24787. [Abstract] [Full Text] [PDF]

				D.J. Haisenleder, L.J. Workman, L.L. Burger, K.W. Aylor, A.C. Dalkin, and J.C. Marshall Gonadotropin Subunit Transcriptional Responses to Calcium Signals in the Rat: Evidence for Regulation by Pulse Frequency Biol Reprod, December 1, 2001; 65(6): 1789 - 1793. [Abstract] [Full Text] [PDF]

				H. W. Lim, L. New, J. Han, and J. D. Molkentin Calcineurin Enhances MAPK Phosphatase-1 Expression and p38 MAPK Inactivation in Cardiac Myocytes J. Biol. Chem., May 4, 2001; 276(19): 15913 - 15919. [Abstract] [Full Text] [PDF]

				K. A. Seta, R. Kim, H.-W. Kim, D. E. Millhorn, and D. Beitner-Johnson Hypoxia-induced Regulation of MAPK Phosphatase-1 as Identified by Subtractive Suppression Hybridization and cDNA Microarray Analysis J. Biol. Chem., November 21, 2001; 276(48): 44405 - 44412. [Abstract] [Full Text] [PDF]