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

1495 14 15146 4 24586 document 15146 Leszczynska11PhD.pdf application/pdf cd0b14bd2b5b3510e6b0571b41646607 MD5 5205815 2011-09-21 10:53:26 http://etheses.bham.ac.uk//id/eprint/1495/1/Leszczynska11PhD.pdf 1495 1 1 application/pdf application/pdf en public

Leszczynska11PhD.pdf

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http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/15146 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/15146 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/15146 archive 4031 disk0/00/00/14/95 2011-09-21 10:53:35 2019-01-23 09:54:18 2011-09-21 10:53:35 thesis show 0 Leszczynska Katarzyna Heath Victoria L Bicknell Roy ftp://ubira.bham.ac.uk/eTheses/1495_Leszczynska/ University of Birmingham Signalling and function of the small Rho GTPase RhoJ in endothelial cells unpub QR180 10col_mede The published paper in the Appendix is available at http://eprints.bham.ac.uk/634/ 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with βPIX and GIT1 and is activated by pro-angiogenic factors. 2011-07 2011-07 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties.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. public 216 University of Birmingham School of Immunity and Infection d_ph na 2011-07 graduation