Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.707618
Title: The regulation of cell signalling by LAR protein tyrosine phosphatase
Author: Sarhan, Adil Rashid
ISNI:       0000 0004 6063 024X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
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Abstract:
Signal transduction pathways are mainly depending on phosphorylation events, which are controlled by the activity of phosphatases and kinases. Although kinases have been widely studied, however, much less is known about the contribution of phosphatases to the regulation of cell signalling pathways. Leukocyte common antigen-related protein (LAR) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases (RPTPs). LAR is involved the regulation of a number of receptor tyrosine kinases (RTKs) including platelet-derived growth factor receptor (PDGFβR). To gain insight into the signaling pathways regulated by LAR, including those that are PDGF-dependent, we have carried out the first systematic analysis of LAR-regulated signal transduction using SILAC-based quantitative proteomic and phosphoproteomic techniques. The differential phosphorylation between wild-type mouse embryo fibroblasts (MEFs) and MEFs in which the LAR cytoplasmic phosphatase domains had been deleted (LARΔP) was analysed. A significant change in abundance of phosphorylation on 270 phosphorylation sites from 205 proteins was associated with the lack of LAR phosphatase activity. Gene ontology analysis revealed an enrichment of LAR-mediated phosphorylation events on proteins involved in many signalling transduction pathways including those regulating the actin cytoskeleton, cell adhesion, endocytosis and cell metabolism. Analysis of putative kinases upstream of LAR-dependent phosphorylation events revealed a role for LAR in regulating signalling through mTOR and JNK. In summary, this thesis identifies an important role for LAR phosphatase in the regulation of signal transduction, cell adhesion and cell metabolism.
Supervisor: Not available Sponsor: Higher Committee for Education Development in Iraq
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.707618  DOI: Not available
Keywords: Q Science (General) ; QH301 Biology ; QH426 Genetics
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