Bond, Michael Edward (2012) Ras signalling in the fission yeast Schizosaccharomyces pombe. PhD thesis, University of Warwick.

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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 or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Cellular signal transduction, Schizosaccharomyces pombe -- Physiology, Guanosine triphosphatase
Date:	February 2012
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Publication Status:	Unpublished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
URI:	http://wrap.warwick.ac.uk/id/eprint/46013

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