Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555230
Title: Investigating the differential properties of the Drosophila JAK/STAT pathway ligands
Author: Wright, Victoria M.
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2011
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Abstract:
The JAK/STAT signalling cascade in vertebrates is activated in response to multiple cytokines and growth factors. By contrast, the Drosophila genome encodes for only three related JAK/STAT ligands, Upd, Upd2 and Upd3. It is hoped that identifying the differences in signalling stimulated by these three Updlike ligands will ultimately lead to a greater understanding of this disease-related pathway and its roles in development. Here, the analysis of the least well characterised of the Upd-like ligands, Upd3, is described. Upd3 is revealed as a secreted molecule that can activate JAK/STAT signalling both in tissue culture systems and in vivo. Also, potential sites of Upd3 expression are identified in both the adult Drosophila ovary and testis, in addition to expression in the larval eye disc and wing disc. Quantification of each of the Upd-like ligands in conditioned media allowed the ability of equal amounts of each ligand to be assessed for activation of the JAK/STAT pathway, revealing that Upd is the most potent ligand in this system. Furthermore, mixing of ligands in conditioned media revealed that the Upd-like ligands do not appear to act in a synergistic manner to activate signalling. In addition, RNAi screens were utilised in Drosophila KC167 cells to determine novel regulators of JAK/STAT signalling. Kinome and phosphatome screening identified 39 kinases and 10 phosphatases as potential modulators of the JAKISTAT pathway in response to stimulation by all three of the Upd-like ligands. Several of the hits identified as acting downstream of the Jak kinase, Hop, were screened for effects on JAK/STAT-mediated tumour formation in vivo. Of those screened, RNAi targeting, PPP4R2r, CG8878 and par-l were found to have significant effects on tumour formation, suggesting a role in JAK/STAT modulation and haematopoiesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.555230  DOI: Not available
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