Characterization of SHP-1 protein tyrosine phosphatase transcripts, protein isoforms and phosphatase activity in epithelial cancer cells.

Abstract

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.

• Authors: Sevan Evren, Simmy Wan, Xue-Zhong Ma, Soad Fahim, Nayha Mody, Darinka Sakac, Tianru Jin, Donald R Branch
• Journal: Genomics (Genomics) 2013 Nov-Dec Vol. 102 Issue 5-6 Pg. 491-9 ISSN: 1089-8646 [Electronic] United States
• PMID: 24100145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Isoenzymes
• RNA, Untranslated
• Protein Tyrosine Phosphatase, Non-Receptor Type 6

Topics

• Alternative Splicing
• Cell Line, Tumor
• Exons
• Frameshift Mutation
• HEK293 Cells
• Humans
• Isoenzymes (chemistry, genetics, metabolism)
• Jurkat Cells
• MCF-7 Cells
• Neoplasms, Glandular and Epithelial (genetics, metabolism)
• Promoter Regions, Genetic
• Protein Binding
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 (chemistry, genetics, metabolism)
• RNA, Untranslated (genetics, metabolism)