Identification and characterization of two novel low-molecular-weight dual specificity phosphatases.
We have cloned and characterized two novel human low molecular weight dual specificity phosphatases (LMW-DSPs). Both genes are expressed exclusively in the testis, but are not altered in any of several disease states examined. Transfection into COS cells indicates that both proteins are expressed in the nucleus and the cytoplasm. Both proteins are able to dephosphorylate the phosphotyrosine analog pNPP in vitro and can be inhibited by sodium orthovanadate. In vitro experiments also demonstrate that both DSPs can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine. However, when co-transfected with MAPKs into COS cells, the novel DSPs exhibited no detectable in vivo activity against MAPKs under our conditions. Our data suggest that these novel LMW-DSPs might belong to a new subclass of testis-specific proteins that act independently of the MAPK signal transduction cascade and do not depend on N-terminal docking regions for substrate binding.
Hood
Kristin L
KL
Metabolic and Respiratory Diseases, Wyeth Research, T4007, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.
Tobin
James F
JF
Yoon
Christina
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D018076:DNA, Complementary; D054637:Dual-Specificity Phosphatases; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology; D014162:Transfection
D018076:DNA, Complementary; D010744:Phosphoric Monoester Hydrolases; C473895:DUSP18 protein, human; C469303:DUSP21 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases