Regulation of cell metabolism by LAR Phosphatase

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Leucocyte common antigen-related protein (LAR; also known as PTPRF) is a widely expressed membrane bound protein tyrosine phosphatase. LAR is comprised of an extracellular region containing multiple immunoglobulin and fibronectin type III adhesion domains, a single transmembrane domain, and two intracellular phosphatase domains. Previous work in cell lines and in LAR-knockout mice has revealed potential roles for LAR in axon guidance, diabetes, neuron degeneration, and abnormal development of mammary glands. Recently, we have used a SILAC-based proteomics approach to analyse signalling in mouse embryo fibroblasts (MEFs) and in MEFs expressing a form of LAR lacking the two intracellular phosphatase domains (LARP). Using this approach we have identified significant changes to the proteome in cells lacking LAR phosphatase activity. GO Term analysis of proteins significantly up- or down-regulated in LARP cells revealed a striking enrichment of proteins involved in cell metabolism. The aims of this project are to investigate the mechanism by which LAR regulates the abundance of these metabolic proteins, and to examine the biological consequences of this regulation by examining distinct metabolic signalling pathways.