Document Detail


Phosphorylation networks regulating JNK activity in diverse genetic backgrounds.
MedLine Citation:
PMID:  18927396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have succeeded in providing parts lists of the essential components of signaling networks, they typically do not provide much insight into the hierarchical and functional relations that exist among these components. We describe a high-throughput screen in which we used RNA interference to systematically inhibit two genes simultaneously in 17,724 combinations to identify regulators of Drosophila JUN NH(2)-terminal kinase (JNK). Using both genetic and phosphoproteomics data, we then implemented an integrative network algorithm to construct a JNK phosphorylation network, which provides structural and mechanistic insights into the systems architecture of JNK signaling.
Authors:
Chris Bakal; Rune Linding; Flora Llense; Elleard Heffern; Enrique Martin-Blanco; Tony Pawson; Norbert Perrimon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  322     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-17     Completed Date:  2008-11-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-6     Citation Subset:  IM    
Affiliation:
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02215, USA. cbakal@receptor.med.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Cell Line
Computational Biology
Drosophila / enzymology*,  genetics
Drosophila Proteins / genetics,  metabolism*
Fluorescence Resonance Energy Transfer
Genes, Insect*
JNK Mitogen-Activated Protein Kinases / genetics,  metabolism*
MAP Kinase Signaling System*
Metabolic Networks and Pathways
Phosphorylation
Proteomics
RNA Interference
Signal Transduction
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Drosophila Proteins; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

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