Structural organization of the rat mitogen-activated protein kinase phosphatase 2 gene

Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are dual specif icity protein phosphatases that specifically inactivate MAPKs. Regulated ex pression of MKPs plays a key role in determining their physiological functi on. However, little is known about the molecular mechanism of the activatio n of MKP genes. In this study, we cloned the rat MKP-2 gene and characteriz ed its structure. The MKP-2 gene has four exons and three introns. The orga nization of exons of the MKP-2 gene is very similar to that of the MKP-1 ge ne, suggesting that MKP-1 and MKP-2 are derived from the same ancestral gen e. We identified multiple transcription start sites (TSSs) for the MKP-2 ge ne. 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 transc riptional activation of the luciferase reporter gene by phorbol ester in GH 3 cells, These results provide essential information about structural organ ization and regulatory sequences of the MKP-2 gene for further investigatio n of the molecular mechanisms of MKP-2 induction by extracellular stimuli. (C) 2001 Published by Elsevier Science B.V. All rights reserved.