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Originally published In Press as doi:10.1074/jbc.M102326200 on June 22, 2001

J. Biol. Chem., Vol. 276, Issue 36, 33319-33327, September 7, 2001
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MAP Kinase Phosphatase-1 Gene Transcription in Rat Neuroendocrine Cells Is Modulated by a Calcium-sensitive Block to Elongation in the First Exon*

Stephan RyserDagger , Silvia TortolaDagger , Goedele van HaasterenDagger , Marco MudaDagger §, Senlin LiDagger , and Werner SchlegelDagger ||

From the Dagger  Fondation pour Recherche Médicales, University of Geneva, Geneva GE 1211, Switzerland

Transcriptional elongation of many eukaryotic, prokaryotic, and viral genes is tightly controlled, which contributes to gene regulation. Here we describe this phenomenon for the MAP kinase phosphatase 1 (MKP-1) immediate early gene. In rat GH4C1 pituitary cells, MKP-1 mRNA is rapidly and transiently induced by the thyrotropin-releasing hormone (TRH) and the epidermal growth factor EGF via transcriptional activation of the gene. Ca2+ signals are necessary for the induction of MKP-1 in response to TRH but not to EGF. Reporter gene analysis with the newly cloned rat promoter sequence shows only limited induction in response to various stimuli, including TRH or EGF. By nuclear run-on assays we demonstrate that in basal conditions, a strong block to elongation in the first exon regulates the MKP-1 gene and that stimulation with either TRH or EGF overcomes the block. Ca2+ signals are important to release the MKP-1 elongation block in a manner similar to the c-fos oncogene. These results suggest that a common mechanism of intragenic regulation may be conserved between MKP-1 and c-fos in mammalian cells.

* This work was supported by the Swiss National Science Foundation Grants 3200-050879.97/1 and 32-61833.00 and by the Fondation pour Recherches Médicales.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF357203.

§ Present address: Serono Reproductive Biology Institute, Randolph, MA.

Present address: Dept. of Medicine, University of Texas Health Science Center, San Antonio, TX.

|| To whom correspondence should be addressed: Fondation pour Recherche Médicales, 64 av. de la Roseraie, University of Geneva, 1211 Geneva, Switzerland. Tel.: 41-22-3823811; Fax: 41-22-3475979; E-mail: werner.schlegel@medecine.unige.ch.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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