Document Detail

Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction.
MedLine Citation:
PMID:  21454597     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-16     Completed Date:  2011-07-26     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18190-201     Citation Subset:  IM    
Copyright Information:
© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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MeSH Terms
Cell Line
Extracellular Signal-Regulated MAP Kinases / genetics,  metabolism*
MAP Kinase Signaling System / physiology*
Nerve Tissue Proteins / genetics,  metabolism*
Neurites / metabolism*
Phosphoproteins / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Phosphoproteins; EC Signal-Regulated MAP Kinases

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