Regulation of platelet derived growth factor signaling by leukocyte common antigen-related (LAR) protein tyrosine phosphatase: a quantitative phosphoproteomics study

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dc.contributor.authorSarhan, Adil R.
dc.contributor.authorPatel, Trushar R.
dc.contributor.authorCreese, Andrew J.
dc.contributor.authorTomlinson, MIchael G.
dc.contributor.authorHellberg, Carina
dc.contributor.authorHeath, John K.
dc.contributor.authorHotchin, Neil A.
dc.contributor.authorCunningham, Debbie L.
dc.date.accessioned2024-08-06T20:30:49Z
dc.date.available2024-08-06T20:30:49Z
dc.date.issued2016
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractIntracellular signaling 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 signaling 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 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. We haveanalyzed 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 because of 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 signaling.
dc.identifier.citationSarhan, A. R., Patel, T. R., Creese, A. J., Tomlinson, M. G., Hellberg, C., Heath, J. K., Hotchin, N. A., & Cunningham, D. L. (2016). Regulation of platelet derived growth factor signaling by leukocyte common antigen-related (LAR) protein tyrosine phosphatase: A quantitative phosphoproteomics study. Molecular & Cellular Proteomics, 15(6), 1823-1836. https://doi.org/10.1074/mcp.M115.053652
dc.identifier.urihttps://hdl.handle.net/10133/6838
dc.language.isoen
dc.publisherElsevier
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Birmingham
dc.publisher.institutionUniversity of Lethbridge
dc.subjectLeukocyte common antigen-related protein
dc.subjectLAR
dc.subjectPhosphatase
dc.subjectCell signaling
dc.subjectSignaling pathways
dc.subjectPlatelet
dc.subject.lcshLeukocytes
dc.subject.lcshPhosphatases
dc.titleRegulation of platelet derived growth factor signaling by leukocyte common antigen-related (LAR) protein tyrosine phosphatase: a quantitative phosphoproteomics study
dc.typeArticle
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