MAP Kinase Phosphatase-1 Gene Transcription in Rat Neuroendocrine Cells Is Modulated by a Calcium-sensitive Block to Elongation in the First Exon

Autor: Goedele van Haasteren, Senlin Li, Silvia Tortola, Marco Muda, Werner Schlegel, Stephan Ryser
Rok vydání: 2001
Předmět:
Transcriptional Activation
Time Factors
Transcription
Genetic

Molecular Sequence Data
Cell Cycle Proteins
Biology
Biochemistry
Gene Expression Regulation
Enzymologic

Immediate-Early Proteins
Exon
Genes
Reporter

Epidermal growth factor
Protein Phosphatase 1
Sequence Homology
Nucleic Acid

Phosphoprotein Phosphatases
Animals
RNA
Messenger

Cloning
Molecular

Promoter Regions
Genetic

Thyrotropin-Releasing Hormone
Molecular Biology
Gene
Cells
Cultured

Cell Nucleus
Neurons
Regulation of gene expression
Reporter gene
Messenger RNA
Base Sequence
Epidermal Growth Factor
Reverse Transcriptase Polymerase Chain Reaction
Dual Specificity Phosphatase 1
Exons
Cell Biology
Blotting
Northern

Molecular biology
Introns
Rats
Blotting
Southern

MAP kinase phosphatase
Calcium
Protein Tyrosine Phosphatases
Proto-Oncogene Proteins c-fos
Immediate early gene
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of Biological Chemistry. 276:33319-33327
ISSN: 0021-9258
DOI: 10.1074/jbc.m102326200
Popis: 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.
Databáze: OpenAIRE