PTP NE-6: a brain-enriched receptor-type protein tyrosine phosphatase with a divergent catalytic domain.
A receptor-type protein tyrosine phosphatase, PTP NE-6, was identified from rat olfactory epithelial cDNA and cloned from a rat brain cDNA library. PTP NE-6 mRNA is abundant in brain and expressed at lower levels in olfactory tissue and adrenal gland. In situ hybridization demonstrates that PTP NE-6 mRNA is expressed throughout the brain, with highest levels in the medial habenula and at intermediate levels in layer IV of cortex, medial geniculate nucleus, inferior colliculus, hypothalamus, and thalamus. The predicted amino acid sequence demonstrates that PTP NE-6 contains a single catalytic domain that diverges from the consensus protein tyrosine phosphatase catalytic domain by expressing an aspartate instead of the conserved alanine residue in the catalytic site. Recombinantly expressed PTP NE-6 does not exhibit detectable phosphatase activity. Upon mutation of the aspartate to the consensus alanine, phosphatase activity toward p-nitrophenyl phosphate is observable with a k(cat) value of 3.7 s(-1) and a Km of 980 microM. These data demonstrate that the inactivity of native PTP NE-6 toward p-nitrophenyl phosphate is due to the divergent aspartate in the catalytic site and not to variant amino acids within the phosphatase domain.
Fitzgerald
L R
LR
University of Maryland at Baltimore, Department of Anatomy and Neurobiology, U.S.A.
Walton
K M
KM
Dixon
J E
JE
Largent
B L
BL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D014018:Tissue Distribution
D017027:Protein Tyrosine Phosphatases; C105576:Ptprn2 protein, rat; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8