Studies of variant SHP-1 protein tyrosine phosphatases in human epithelial cells.
Published: 2004
Language: eng
Number of pages: 158
Description: The SH2 domain containing protein tyrosine phosphatase SHP-1 negatively regulates hematopoietic cell growth; however, its function in epithelial cells remains unclear. SHP-1 is auto-inhibited by an intramolecular interaction between its N-SH2 domain and C-terminus. Using human epithelial cancer cell lines we detected alternatively-spliced in-frame SHP-1 transcripts that utilize either promoter 1 or 2, have a partial (exon 3) or complete (exons 3 & 4) deletion of the N-SH2 domain, and demonstrate intron 2 retention (non-coding). We showed that exon 3 deleted SHP-1 protein is difficult to express and may have a shortened half-life, and SHP-1 lacking the entire N-SH2 domain has increased phosphatase activity. Both exon(s) deleted SHP-1 exhibits unusual protein-binding patterns. Multiple SHP-1 proteins with sizes corresponding to those predicted by alternate transcripts were detected in SK-BR-3 human breast cancer cells. With unregulated activities and differential protein-binding patterns, variant SHP-1 may contribute to epithelial tumorigenesis by modulating normal signaling pathways.
Notes: Adviser:  Donald Branch.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0830.

MICR copy on microfiche (2 microfiches).