MAP kinase phosphatase-1 gene transcription in rat neuroendocrine cells is modulated by a calcium-sensitive block to elongation in the first exon.
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. Ca(2+) 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. Ca(2+) 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.
Ryser
S
S
Fondation pour Recherche Médicales, University of Geneva, Geneva GE 1211, Switzerland.
Tortola
S
S
van Haasteren
G
G
Muda
M
M
Li
S
S
Schlegel
W
W
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002118:Calcium / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D054638:Dual Specificity Phosphatase 1; D004815:Epidermal Growth Factor / Q000378:metabolism; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; D002118:Calcium