Isolation, sequence and expression of a novel mouse brain cDNA, mIA-2, and its relatedness to members of the protein tyrosine phosphatase family.
This study describes the isolation of a putative transmembrane protein tyrosine phosphatase (PTP), mIA-2, from a mouse brain cDNA library. The cDNA encodes 979 amino acids containing a unique extracellular domain and a single intracellular catalytic domain. Expression of mIA-2 was found primarily in the central nervous system and in neuroendocrine cells. The sequence shares a high degree of homology with its human counterpart (92% identity), especially in the intracellular domain, which shows 99.3% identity between the two species. In both human and mouse IA-2, several substitutions were found in the highly conserved regions including an Ala to Asp substitution in the core sequence. Bacterial expression of a glutathione S-transferase fusion protein showed that mIA-2 had no enzyme activity with conventional substrates such as Raytide, myelin basic protein, angiotensin, RR-src and pNpp. When tested with the total tyrosine-phosphorylated cellular proteins isolated on an anti-phosphotyrosine antibody column, it also showed little, if any, enzyme activity. These findings suggest that mIA-2 is a new member of the transmembrane PTP family that either has very narrow substrate specificity perhaps requiring post-translational modification for enzyme activity or has a still unknown biological function.
Laboratory of Oral Medicine, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
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D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001419:Bacteria / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001324:Autoantigens; D018076:DNA, Complementary; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; C516862:PTPRN protein, human; D017027:Protein Tyrosine Phosphatases; C516863:Ptprn protein, mouse; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8