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The effects of phosphorylation on the regulation of Ras localisation in eukaryotic cells

Piper-Brown, Elliot (2015) The effects of phosphorylation on the regulation of Ras localisation in eukaryotic cells. Master of Science by Research (MScRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.50855) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:50855)

Language: English

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Ras proteins are small GTPases that function as regulatory switches linking external environmental stimuli with intracellular effectors to control cell growth and proliferation. Mutations that lead to the constitutive activation of Ras proteins are associated with the development of several human cancers. The localisation of Ras is crucial for its function and this is controlled by post-translational modifications. The genes encoding Ras proteins are highly conserved and yeast serves as a useful model to study the control of localisation and activation. Serine225 has been implicated as a potential phosphorylation site which affects Ras2p localization in S. cerevisiae. The substitution of serine225 with alanine or glutamate suggests that serine225 plays a key role in Ras2p localisation. Although there is significant sequence divergence outside of the GTPase domain and C terminal CAAX box. Sequence alignment between yeast Ras2 and human N-Ras suggests that serine225 and the surrounding sequence are conserved. This study aims to determine whether phosphorylation of human N-Ras regulates activity and localisation when expressed in yeast cells. We have successfully expressed N-Ras in yeast cells and find that it is targeted to the plasma membrane, suggesting that is correctly processed by yeast cells. Modification of the residue equivalent to yeast Ras2 serine225 in N-Ras leads to senescence in the yeast system suggesting that this conserved serine residue is important for function. As the N-Ras human oncogene is linked to many cancers, especially malignant melanomas, the data collected in this study could potentially provide a greater understanding into the activity and regulation of Ras2p and N-Ras, which could be used to aid in the formulation of new strategies for cancer treatment.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Gourlay, Campbell
DOI/Identification number: 10.22024/UniKent/01.02.50855
Additional information: The author of this thesis has requested that it be held under closed access. We are sorry but we will not be able to give you access or pass on any requests for access. 16/12/2021
Uncontrolled keywords: Cell Biology Ras Cancer Biology Signalling Neuroblastoma N-Ras Ras2
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Users 1 not found.
Date Deposited: 09 Oct 2015 15:00 UTC
Last Modified: 16 Dec 2021 14:19 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Piper-Brown, Elliot.

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