Structural organization of the rat mitogen-activated protein kinase phosphatase 2 gene.
Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are dual specificity protein phosphatases that specifically inactivate MAPKs. Regulated expression of MKPs plays a key role in determining their physiological function. However, little is known about the molecular mechanism of the activation of MKP genes. In this study, we cloned the rat MKP-2 gene and characterized its structure. The MKP-2 gene has four exons and three introns. The organization of exons of the MKP-2 gene is very similar to that of the MKP-1 gene, suggesting that MKP-1 and MKP-2 are derived from the same ancestral gene. We identified multiple transcription start sites (TSSs) for the MKP-2 gene. There is no functional TATA motif in the 5' proximal region of the TSSs. Instead, this region is highly GC-rich and has two putative Sp1 sites. A 1.8 kb 5' flanking region of the MKP-2 gene is sufficient to mediate transcriptional activation of the luciferase reporter gene by phorbol ester in GH3 cells. These results provide essential information about structural organization and regulatory sequences of the MKP-2 gene for further investigation of the molecular mechanisms of MKP-2 induction by extracellular stimuli.
Zhang
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T
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Choy
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M
Jo
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Roberson
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018387:Codon, Initiator; D054637:Dual-Specificity Phosphatases; D005786:Gene Expression Regulation; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D016385:TATA Box; D014162:Transfection
D018387:Codon, Initiator; D054639:Mitogen-Activated Protein Kinase Phosphatases; D054648:Protein Phosphatase 2; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases; C094132:Dusp4 protein, rat; D017027:Protein Tyrosine Phosphatases