Genomics
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2M1, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M1, Canada; Canadian Blood Services, Research and Development, Toronto, ON M5G 2M1, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 2M1, Canada; Toronto General Research Institute, Division of Molecular Therapeutics, Toronto, ON M5G 2M1, Canada.
Published: July 2014
We identified 7 SHP-1 (PTPN6) transcripts using epithelial cancer-derived cell lines. Four were shown to utilize the epithelial promoter 1 to transcribe a full-length, a partial (exon 3) or complete (exons 3 & 4) deletion of the N-SH2 domain, and also a non-coding transcript having a stop codon caused by a frame shift due to intron 2 retention. Three additional transcripts were shown to utilize the hematopoietic promoter 2 to transcribe a full-length, a partial (exon 3) deletion of the N-SH2 domain and a non-coding transcript with intron 2 retention. We show that endogenous proteins corresponding to the open-reading-frame (ORF) transcripts are produced. Using GST-fusion proteins we show that each product of the ORF SHP-1 transcripts has phosphatase activity and isoforms with an N-SH2 deletion have increased phosphatase activity and novel protein-protein interactions. This study is the first to document utilization of promoter 2 by SHP-1 transcripts and a noncoding transcript in human epithelial cells.
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http://dx.doi.org/10.1016/j.ygeno.2013.10.001 | DOI Listing |
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