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

Abstract 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 ar...

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Autores principales:	Adil R. Sarhan, Justyna Szyroka, Shabana Begum, Michael G. Tomlinson, Neil A. Hotchin, John K. Heath, Debbie L. Cunningham
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b0dbe9723e34b89ad5ea75b59b2f907
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spelling	oai:doaj.org-article:0b0dbe9723e34b89ad5ea75b59b2f9072021-12-02T15:05:41ZQuantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration10.1038/s41598-017-04015-x2045-2322https://doaj.org/article/0b0dbe9723e34b89ad5ea75b59b2f9072017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04015-xhttps://doaj.org/toc/2045-2322Abstract 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.Adil R. SarhanJustyna SzyrokaShabana BegumMichael G. TomlinsonNeil A. HotchinJohn K. HeathDebbie L. CunninghamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adil R. Sarhan Justyna Szyroka Shabana Begum Michael G. Tomlinson Neil A. Hotchin John K. Heath Debbie L. Cunningham Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
description	Abstract 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.
format	article
author	Adil R. Sarhan Justyna Szyroka Shabana Begum Michael G. Tomlinson Neil A. Hotchin John K. Heath Debbie L. Cunningham
author_facet	Adil R. Sarhan Justyna Szyroka Shabana Begum Michael G. Tomlinson Neil A. Hotchin John K. Heath Debbie L. Cunningham
author_sort	Adil R. Sarhan
title	Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
title_short	Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
title_full	Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
title_fullStr	Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
title_full_unstemmed	Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
title_sort	quantitative phosphoproteomics reveals a role for collapsin response mediator protein 2 in pdgf-induced cell migration
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0b0dbe9723e34b89ad5ea75b59b2f907
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Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration

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