| Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction. | |
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MedLine Citation:
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PMID: 21454597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis. |
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Authors:
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Yingchun Wang; Feng Yang; Yi Fu; Xiahe Huang; Wei Wang; Xinning Jiang; Marina A Gritsenko; Rui Zhao; Matthew E Monore; Olivier C Pertz; Samuel O Purvine; Daniel J Orton; Jon M Jacobs; David G Camp; Richard D Smith; Richard L Klemke |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-07-26 Revised Date: 2012-09-20 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 18190-201 Citation Subset: IM |
Copyright Information:
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© 2011 by The American Society for Biochemistry and Molecular Biology, Inc. |
Affiliation:
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Department of Pathology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Extracellular Signal-Regulated MAP Kinases / genetics, metabolism* Humans MAP Kinase Signaling System / physiology* Nerve Tissue Proteins / genetics, metabolism* Neurites / metabolism* Phosphoproteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA097022/CA/NCI NIH HHS; GM068487/GM/NIGMS NIH HHS; P41 RR018522-08/RR/NCRR NIH HHS; RR018522/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nerve Tissue Proteins; 0/Phosphoproteins; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
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