Regulation of cell metabolism by LAR Phosphatase

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

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.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1790850 Studentship BB/M01116X/1 03/10/2016 25/12/2020 Carys Angharad Howell
 
Description LAR substrates 
Organisation Babraham Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Molecular cloning of the LAR intracellular domain and validation of mass spectrometry proteomics experiments (completed by the partner) using western blotting
Collaborator Contribution Identification of LAR substrates by immunoprecipitation coupled to mass spectrometry
Impact No current outputs Current outcomes include results of mass spectrometry proteomics experiments which have guided further experiments and validations.
Start Year 2019