HUMAN PROTEIN-TYROSINE-PHOSPHATASE 1C(PTPN6) GENE STRUCTURE - ALTERNATE PROMOTER USAGE AND EXON SKIPPING GENERATE MULTIPLE TRANSCRIPTS

PTPN6, a protein tyrosine phosphatase with two Src homolog-2 domains, is expressed predominantly in cells of the hematopoietic lineage, In a ddition, cDNAs encoding isoforms of the enzyme differing from the latt er at their N-termini have been detected in normal and transformed epi thelial cells. To understand further the regulation and expression of the PTPN6 gene, we have isolated and characterized overlapping human g enomic lambda clones containing the entire locus. The gene, located on chromosome 12, consists of 17 exons spanning 17 kb of DNA. Three nonh ematopoietic PTPN6 transcripts were identified in a variety of cell li nes and were shown to be transcribed from a common promoter. Alternate splicing and exon skipping result in transcripts encoding the two SH2 domains and minor transcripts from which part of or the entire N-term inal SH2 domain coding sequences are missing, The hematopoietic form o f PTPN6 transcript is initiated at a downstream promoter separated by 7 kb from the first. This promoter is active exclusively in cells of t he hematopoietic lineage. Characterization of the 5' ends of the PTPN6 mRNAs by RT-PCR and analysis of the flanking genomic sequences identi fied putative initiation sites within the two promoters. (C) 1995 Acad emic Press, Inc.