Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration

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作者
Adil R. Sarhan
Justyna Szyroka
Shabana Begum
Michael G. Tomlinson
Neil A. Hotchin
John K. Heath
Debbie L. Cunningham
机构
[1] University of Birmingham,School of Biosciences
[2] College of Life Sciences,MRC Protein Phosphorylation and Ubiquitylation Unit
[3] University of Dundee,undefined
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Scientific Reports | / 7卷
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The Platelet Derived Growth Factor (PDGF) family of ligands have well established functions in the induction of cell proliferation and migration during development, tissue homeostasis and interactions between tumours and stroma. However, the mechanisms by which these actions are executed are incompletely understood. Here we report a differential phosphoproteomics study, using a SILAC approach, of PDGF-stimulated mouse embryonic fibroblasts (MEFs). 116 phospho-sites were identified as up-regulated and 45 down-regulated in response to PDGF stimulation. These encompass proteins involved in cell adhesion, cytoskeleton regulation and vesicle-mediated transport, significantly expanding the range of proteins implicated in PDGF signalling pathways. Included in the down-regulated class was the microtubule bundling protein Collapsin Response Mediator Protein 2 (CRMP2). In response to stimulation with PDGF, CRMP2 was dephosphorylated on Thr514, an event known to increase CRMP2 activity. This was reversed in the presence of micromolar concentrations of the protein phosphatase inhibitor okadaic acid, implicating PDGF-induced activation of protein phosphatase 1 (PP1) in CRMP2 regulation. Depletion of CRMP2 resulted in impairment of PDGF-mediated cell migration in an in vitro wound healing assay. These results show that CRMP2 is required for PDGF-directed cell migration in vitro.
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