MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases.
Dual-specificity protein tyrosine phosphatases are a burgeoning family of enzymes, some of which, the MKPs, are implicated in the regulation of mitogen-activated protein (MAP) kinases. MKPs have been shown to reverse the activation of the MAP kinases by hydrolyzing phosphothreonine and phosphotyrosine residues present in the substrates. Here we describe the characterization of a novel member of the MKP family, MKP5. The MKP5 gene, which maps to human chromosome 1q32, is expressed tissue-specifically as two transcripts of approximately 3.4 and 2.4 kb in human liver and skeletal muscle. When expressed in mammalian cells, MKP5 blocks the enzymatic activation of MAP kinases with the selectivity p38 approximately JNK/SAPK >> ERK. Immunoprecipitation of endogenous MAP kinases by the catalytically inactive transfected MKP5 demonstrates that it preferentially binds to the p38 and JNK/SAPK kinases. These findings suggest that the selectivity of this phosphatase may be determined at least in part at the level of substrate binding.
Theodosiou
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A
Section of Gene Function and Regulation, Chester Beatty Laboratories, London, UK.
Smith
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A
Gillieron
C
C
Arkinstall
S
S
Ashworth
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A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D018076:DNA, Complementary; D054637:Dual-Specificity Phosphatases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D054639:Mitogen-Activated Protein Kinase Phosphatases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; C120407:DUSP10 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases