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Signalling and function of the small Rho GTPase RhoJ in endothelial cells

Leszczynska, Katarzyna (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

RhoJ is an endothelial expressed Rho GTPase, and its knock-down impairs endothelial cell (EC) migration and tubulogenesis, increases stress fibre (SF) and focal adhesion (FA) numbers. This work aimed to determine the intracellular localisation of RhoJ, identify its binding partners, test how it is activated and further explore its function in ECs.
Endogenous RhoJ localised to FAs and overexpression of its active mutant (daRhoJ) promoted EC migration, and diminished FA and SF numbers. In addition to FAs, overexpressed RhoJ localised also to endosomes and RhoJ knock-down slightly delayed transferrin recycling. Vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2) and thrombin activated RhoJ in ECs. PAK-interacting exchange factor β (βPIX) and G protein-coupled receptor kinase-interacting target 1 (GIT1), which promote FA disassembly, were identified as RhoJ-binding partners. RhoJ co-localised with these proteins in ECs, and βPIX knock-down and to a lesser extent GIT1 knock-down reduced RhoJ localisation to FAs. Overexpression of daRhoJ increased the amount of GIT1 and βPIX in FAs, and increased the total amount of the βPIX protein in ECs.
In conclusion, RhoJ localises to FAs, promotes EC migration, regulates FA and SF numbers, interacts with βPIX and GIT1 and is activated by pro-angiogenic factors.

Type of Work:Ph.D. thesis.
Supervisor(s):Heath, Victoria L and Bicknell, Roy
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Additional Information:

The published paper in the Appendix is available at http://eprints.bham.ac.uk/634/

Subjects:QR180 Immunology
Institution:University of Birmingham
ID Code:1495
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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