CLONING AND EXPRESSION OF 2 STRUCTURALLY DISTINCT RECEPTOR-LINKED PROTEIN-TYROSINE PHOSPHATASES GENERATED BY RNA PROCESSING FROM A SINGLE-GENE

We describe here the first example of RNA processing generating two fu nctional receptor-linked protein-tyrosine phosphatases (PTP) (protein- tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) that are structurall y distinct within their catalytic domains. Two cDNAs, PTP-P1 and PTP-P S, were isolated from rat pheochromocytoma cells, which encode two rec eptor-linked protein-tyrosine-phosphatases and are produced by alterna tive splicing and differential use of polyadenylation sites. Both cDNA s share an identical extracellular domain and a single transmembrane d omain, but differ within their cytoplasmic regions: PTP-P1 contains tw o tandem repeated PTPase catalytic domains, whereas PTP-PS contains on ly the amino-terminal domain. Bacterial expression of PTPase domains o f both cDNAs demonstrates that PTP-P1 and PTP-PS contain tyrosine-phos phatase activity. PTP-P1 is encoded by three transcripts of approximat ely 8, 6, and 4 kilobases, whereas PTP-PS is encoded by a single 4.8-k ilobase transcript. PTP-P1 (6 kilobases) and PTP-PS are mainly express ed within the brain and in neuronal and endocrine cells. These data su ggest that PTP-P1 and PTP-PS may be involved in neuronal function.