The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system.
We have isolated cDNA clones and deduced the complete amino acid sequence of a large receptor-type protein tyrosine phosphatase containing 2307 amino acids. The human gene encoding this phosphatase, denoted RPTP beta (or PTP zeta), has been localized to chromosome 7q31-33. RPTP beta is composed of a large extracellular domain, a single transmembrane domain, and a cytoplasmic portion with two tandem catalytic domains. We have also cloned a variant of RPTP beta lacking 859 amino acids from the extracellular domain but with intact transmembrane and cytoplasmic domains. Interestingly, the amino-terminal region of the extracellular domain of RPTP beta contains a stretch of 266 amino acids with striking homology to the enzyme carbonic anhydrase. Immunoprecipitation experiments from a human neuroblastoma cell line indicate that the apparent molecular mass of the core and glycosylated forms of RPTP beta are approximately 250 and 300 kDa, respectively. Northern blot analysis shows that RPTP beta is strictly expressed in the central nervous system. In situ hybridization was used to further localize the expression to different 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, RPTP beta represents the first mammalian tyrosine phosphatase whose expression is restricted to the nervous system. The high level of expression of RPTP beta transcripts in the ventricular and subventricular zones of the embryonic mouse brain suggests the importance of this tyrosine phosphatase in the development of the central nervous system.
Department of Pharmacology, New York University Medical Center, New York 10016.
J B
JB
Levy
P D
PD
Canoll
O
O
Silvennoinen
G
G
Barnea
B
B
Morse
A M
AM
Honegger
J T
JT
Huang
L A
LA
Cannizzaro
S H
SH
Park
T
T
Druck
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D014644:Genetic Variation; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011689:Purkinje Cells / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D011956:Receptors, Cell Surface; D004247:DNA; D017027:Protein Tyrosine Phosphatases