MOLECULAR-CLONING AND CHROMOSOMAL LOCALIZATION OF A HUMAN GENE HOMOLOGOUS TO THE MURINE R-PTP-KAPPA, A RECEPTOR-TYPE PROTEIN-TYROSINE-PHOSPHATASE

Tyrosine phosphorylation of proteins plays an important role in cellul ar signaling and many cellular activities. The levels of cellular phos phorylation are reversibly controlled by protein tyrosine kinases and protein tyrosine phosphatases. The murine R-PTP-kappa, a receptor-type protein tyrosine phosphatase, has recently been cloned (Jiang et al. (1993) Mol. Cell. Biol. 13, 2942-2951). In order to identify the prote in tyrosine phosphatases critical to the cellular signal transduction in human keratinocytes, a polymerase chain reaction (PCR)-based strate gy was employed, and we have cloned a human homologue of the murine R- PTP-kappa Here, we report the isolation of a complementary DNA encodin g a human R-PTP-kappa. Of the several overlapping cDNA clones, one clo ne, which we originally termed p55-7, was found to encode a transmembr ane protein of 1440 amino acids and was highly conserved with murine R -PTP-kappa with 98% identity at the amino-acid levels. The human R-PTP -kappa gene was localized to chromosome 6 by southern hybridization of DNA from a rodent/human somatic cell mapping panel. Northern blot ana lysis of RNA from several human tissues revealed, like the murine R-PT P-kappa, the presence of a major mRNA of approx. 7.0 kb and a minor mR NA of approx. 5.3 kb. In contrast to the expression of murine R-PTP-ka ppa which was highly expressed in liver and kidney, the human R-PTP-ka ppa was predominantly expressed in spleen, prostate, and ovary. Howeve r, the transcripts were detectable at various levels in all examined t issues (thymus, testis, small intestine, and colon) except for PBL (pe ripheral blood leukocytes). In addition, human R-PTP-kappa displayed a restricted pattern of expression among a series of cell lines, and wa s apparently expressed in an epidermal cells and cell lines (human nor mal keratinocytes, HaCaT, and A431), but was not detectable in other c ell lines tested after longer exposure.