MAP kinase phosphatase-1 gene transcription in rat neuroendocrine cells ismodulated 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 descr ibe this phenomenon for the MAP kinase phosphatase 1 (MKP-1) immediate earl y gene. In rat GH4C1 pituitary cells, MKP-1 mRNA is rapidly and transiently induced by the thyrotropin-releasing hormone (TRH) and the epidermal growt h factor EGF via transcriptional activation of the gene. Ca2+ signals are n ecessary for the induction of MKP-1 in response to TRH but not to EGF. Repo rter gene analysis with the newly cloned rat promoter sequence shows only l imited induction in response to various stimuli, including TRH or EGF. By n uclear run-on assays we demonstrate that in basal conditions, a strong bloc k to elongation in the first exon regulates the MKP-1 gene and that stimula tion 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 onc ogene. These results suggest that a common mechanism of intragenic regulati on may be conserved between MKP-1 and c-fos in mammalian cells.