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Ras signalling in the fission yeast Schizosaccharomyces pombe
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Bond, Michael Edward (2012) Ras signalling in the fission yeast Schizosaccharomyces pombe. PhD thesis, University of Warwick.
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WRAP_THESIS_Bond_2012.pdf - Submitted Version Download (59Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b2565916~S1
Abstract
Ras signalling is vital to many cellular processes. Ras proteins mediate a
vast array of cellular signalling networks, and are conserved from humans to
unicellular eukaryotes. The study of ras signalling in higher eukaryotes presents
a number of technical challenges, due to the presence of multiple ras isoforms,
regulatory proteins and activators. The fission yeast Sz. pombe represents an
ideal system for the investigation of ras signalling, as it contains a single, nonessential
ras protein (Ras1). In addition, Ras1 is involved in the regulation of
a number of downstream pathways.
A number of studies in recent years have highlighted the role of subcellular
localisation in ras signalling output. The localisation of Ras1 in Sz. pombe
has also been described as key in effector selection, with Ras1 at the plasma
membrane regulating mating and Ras1 at the endomembranes regulating cell
morphology. This thesis describes a series of studies utilising Ras1 mutants
and chimeric Ras1 proteins which display differing localisation patterns to determine
the role of Ras1 localisation in signalling. The data presented herein
support the notion of a revised model for the role of Ras1 localisation in signalling,
suggesting that the localisation of Ras1 to the plasma membrane is
key to all signalling events downstream of Ras1.
This thesis also describes the characterisation of oncogenic mutants of Ras1,
demonstrating the importance of signalling magnitude in functional output. In
addition, the importance of Ras1 regulation in cell viability and chromosome
stability is also demonstrated. Finally, the functional expression of three human
ras isoforms is described, validating the use of Sz. pombe as a model
system for the heterologous expression of human ras signalling components.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QP Physiology | ||||
Library of Congress Subject Headings (LCSH): | Cellular signal transduction, Schizosaccharomyces pombe -- Physiology, Guanosine triphosphatase | ||||
Official Date: | February 2012 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Ladds, Graham Robert ; Davey, John | ||||
Extent: | xxviii, 301 leaves : ill., charts | ||||
Language: | eng |
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