Journal article
Differential Regulation of Mitogen-Activated Protein Kinase-Responsive Genes by the Duration of a Calcium Signal
Molecular endocrinology (Baltimore, Md.), Vol.14(10), pp.1570-1582
10/01/2000
DOI: 10.1210/mend.14.10.0529
PMID: 11043573
Abstract
Abstract
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.
Details
- Title: Subtitle
- Differential Regulation of Mitogen-Activated Protein Kinase-Responsive Genes by the Duration of a Calcium Signal
- Creators
- Paul L Durham - 1Department of Physiology and Biophysics University of Iowa Iowa City, Iowa 52242Andrew F Russo - 1Department of Physiology and Biophysics University of Iowa Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.14(10), pp.1570-1582
- DOI
- 10.1210/mend.14.10.0529
- PMID
- 11043573
- NLM abbreviation
- Mol Endocrinol
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 10/01/2000
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984013202502771
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