Bidirectional co-signalling between the erythropoietin receptor and stem cell derived tyrosine kinase.
Published: 2006
Language: eng
Number of pages: 118
ISBN-13: 9780494214473
Description: Friend virus-mediated erythroleukemia is a well-established model of murine oncogenesis. Key molecular events include constitutive activation of the EPO-R as well as expression and kinase activity of Sf-STK. While both receptors are essential in Friend disease, it is unknown whether Sf-STK modulates EPO-R-mediated signalling.In this study we show constitutive co-immunoprecipitation of EPO-R with both Sf-STK and STK. Furthermore, we demonstrate that EPO-R and STK participate in bi-directional cross-talk and co-stimulation, resulting in enhanced tyrosine phosphorylation of both receptors. Unlike EPO-R, STK ligand-independent tyrosine phosphorylation was dependent on its kinase activity. STK was shown to co-regulate specific EPO-dependent signalling pathways. Co-operative phosphorylation was observed for ERK 1/2 and PKB, but not JAK2, STAT1, STAT5, SAPK and p38, in a GAB2-dependent manner. Additionally, STK expression enhanced EPO-regulated expression of cis and socs-3. This work suggests that Sf-STK contributes to Friend disease by enhancing proliferative and survival signals downstream of the EPO-R.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1353.

Thesis (M.Sc.)--University of Toronto, 2006.

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