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 homology-2 domains, is expressed predominantly in cells of the hematopoietic lineage. In addition, cDNAs encoding isoforms of the enzyme differing from the latter at their N-termini have been detected in normal and transformed epithelial cells. To understand further the regulation and expression of the PTPN6 gene, we have isolated and characterized overlapping human genomic λ clones containing the entire locus. The gene, located on chromosome 12, consists of 17 exons spanning 17 kb of DNA. Three nonhematopoietic PTPN6 transcripts were identified in a variety of cell lines 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-terminal SH2 domain coding sequences are missing. The hematopoietic form of PTPN6 transcript is initiated at a downstream promoter separated by 7 kb from the first. This promoter is active exclusively in cells of the hematopoietic lineage. Characterization of the 5′ ends of the PTPN6 mRNAs by RT-PCR and analysis of the flanking genomic sequences identified putative initiation sites within the two promoters.