THE CLONING OF A RECEPTOR-TYPE PROTEIN-TYROSINE PHOSPHATASE EXPRESSEDIN THE CENTRAL-NERVOUS-SYSTEM

We have isolated cDNA clones and deduced the complete amino acid seque nce of a large receptor-type protein tyrosine phosphatase containing 2 307 amino acids. The human gene encoding this phosphatase, denoted RPT Pbeta (or PTPzeta), has been localized to chromosome 7q31-33. RPTPbeta is composed of a large extracellular domain, a single transmembrane d omain, and a cytoplasmic portion with two tandem catalytic domains. We have also cloned a variant of RPTPbeta lacking 859 amino acids from t he extracellular domain but with intact transmembrane and cytoplasmic domains. Interestingly, the amino-terminal region of the extracellular domain of RPTPbeta contains a stretch of 266 amino acids with strikin g homology to the enzyme carbonic anhydrase. Immunoprecipitation exper iments from a human neuroblastoma cell line indicate that the apparent molecular mass of the core and glycosylated forms of RPTPbeta are app roximately 250 and 300 kDa, respectively. Northern blot analysis shows that RPTPbeta is strictly expressed in the central nervous system. In situ hybridization was used to further localize the expression to dif ferent regions of the adult brain including the Purkinje cell layer of the cerebellum, the dentate gyrus, and the subependymal layer of the anterior horn of the lateral ventricle. Hence, RPTPbeta represents the first mammalian tyrosine phosphatase whose expression is restricted t o the nervous system. The high level of expression of RPTPbeta transcr ipts in the ventricular and subventricular zones of the embryonic mous e brain suggests the importance of this tyrosine phosphatase in the de velopment of the central nervous system.