Regulation of platelet derived growth factor signalling by LAR protein tyrosine phosphatase: a quantitative phosphoproteomics study

Adil Rashid Sarhan Almuntafeky, Trushar Patel, Andrew Creese, Michael Tomlinson, Carina Hellberg, John Heath, Neil Hotchin, Debbie Cunningham

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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Intracellular signalling pathways are reliant on protein phosphorylation events that are controlled by a balance of kinase and phosphatase activity. Although kinases have been extensively studied, the role of phosphatases in controlling specific cell signalling pathways has been less so. Leukocyte common antigen-related protein (LAR) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases (RPTPs). LAR is known to regulate the activity of a number of receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR). To gain insight into the signalling 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. We have analysed differential phosphorylation between wild-type mouse embryo fibroblasts (MEFs) and MEFs in which the LAR cytoplasmic phosphatase domains had been deleted (LARΔP), and found a significant change in abundance of phosphorylation on 270 phosphosites from 205 proteins due to the absence of the phosphatase domains of LAR. Further investigation of specific LAR-dependent phosphorylation sites and enriched biological processes reveal that LAR phosphatase activity impacts on a variety of cellular processes, most notably regulation of the actin cytoskeleton. Analysis of putative upstream kinases that may play an intermediary role between LAR and the identified LAR-dependent phosphorylation events has revealed a role for LAR in regulating mTOR and JNK signalling.
Original languageEnglish
Pages (from-to)1823-1836
Number of pages14
JournalMolecular and Cellular Proteomics
Issue number6
Early online date13 Apr 2016
Publication statusPublished - 1 Jun 2016


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