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
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机构:University of Birmingham,School of Biosciences
Adil R. Sarhan
Justyna Szyroka
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机构:University of Birmingham,School of Biosciences
Justyna Szyroka
Shabana Begum
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机构:University of Birmingham,School of Biosciences
Shabana Begum
Michael G. Tomlinson
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机构:University of Birmingham,School of Biosciences
Michael G. Tomlinson
Neil A. Hotchin
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机构:University of Birmingham,School of Biosciences
Neil A. Hotchin
John K. Heath
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机构:University of Birmingham,School of Biosciences
John K. Heath
Debbie L. Cunningham
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机构:University of Birmingham,School of Biosciences
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
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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.
机构:
IRCCS AOU San Martino IST, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Appolloni, Irene
Curreli, Sebastiano
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Univ Genoa, Dept Expt Med DiMES, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Curreli, Sebastiano
Caviglia, Sara
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Univ Genoa, Dept Expt Med DiMES, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Caviglia, Sara
Barilari, Manuela
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IRCCS AOU San Martino IST, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Barilari, Manuela
Gambini, Eleonora
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Univ Genoa, Dept Expt Med DiMES, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Gambini, Eleonora
Pagano, Aldo
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机构:
IRCCS AOU San Martino IST, I-16132 Genoa, Italy
Univ Genoa, Dept Expt Med DiMES, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Pagano, Aldo
Malatesta, Paolo
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机构:
IRCCS AOU San Martino IST, I-16132 Genoa, Italy
Univ Genoa, Dept Expt Med DiMES, I-16132 Genoa, ItalyIRCCS AOU San Martino IST, I-16132 Genoa, Italy
Malatesta, Paolo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,
2012,
13
(11):
: 14667
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14678
机构:
Department of Neurology, University Medicine G?ttingen
Department of Neurobiology, Beijing Institute for Brain Disorders and Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical UniversityDepartment of Neurology, University Medicine G?ttingen
Jian-Nan Zhang
Jan C.Koch
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机构:
Department of Neurology, University Medicine G?ttingenDepartment of Neurology, University Medicine G?ttingen
机构:
Univ Med Gottingen, Dept Neurol, Gottingen, Germany
Capital Med Univ, Dept Neurobiol, Beijing Inst Brain Disorders, Beijing, Peoples R China
Capital Med Univ, Key Lab Neurodegenerat Dis, Minist Educ, Beijing, Peoples R ChinaUniv Med Gottingen, Dept Neurol, Gottingen, Germany
机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Williams, Holly C.
Martin, Alejandra San
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Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Martin, Alejandra San
Adamo, Candace M.
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机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Adamo, Candace M.
Seidel-Rogol, Bonnie
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机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Seidel-Rogol, Bonnie
Pounkova, Lily
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机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Pounkova, Lily
Datla, Srinivasan Raju
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机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Datla, Srinivasan Raju
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机构:
Lassegue, Bernard
Bear, James E.
论文数: 0引用数: 0
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机构:
Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC USA
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA
Bear, James E.
Griendling, Kathy
论文数: 0引用数: 0
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机构:
Emory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USAEmory Univ, Div Cardiol, Sch Med, Dept Med, Atlanta, GA 30322 USA