Document Detail


Deciphering signaling outcomes from a system of complex networks.
MedLine Citation:
PMID:  19454649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular signal transduction machinery integrates information from multiple inputs to actuate discrete cellular behaviors. Interaction complexity exists when an input modulates the output behavior that results from other inputs. To address whether this machinery is iteratively complex--that is, whether increasing numbers of inputs produce exponential increases in discrete cellular behaviors--we examined the modulated secretion of six cytokines from macrophages in response to up to five-way combinations of an agonist of Toll-like receptor 4, three cytokines, and conditions that activated the cyclic adenosine monophosphate pathway. Although all of the selected ligands showed synergy in paired combinations, few examples of nonadditive outputs were found in response to higher-order combinations. This suggests that most potential interactions are not realized and that unique cellular responses are limited to discrete subsets of ligands and pathways that enhance specific cellular functions.
Authors:
Robert C Hsueh; Madhusudan Natarajan; Iain Fraser; Blake Pond; Jamie Liu; Susanne Mumby; Heping Han; Lily I Jiang; Melvin I Simon; Ronald Taussig; Paul C Sternweis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-19
Journal Detail:
Title:  Science signaling     Volume:  2     ISSN:  1937-9145     ISO Abbreviation:  Sci Signal     Publication Date:  2009  
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-10-27     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101465400     Medline TA:  Sci Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  ra22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Animals
Cell Line
Chemokine CCL3 / metabolism,  secretion
Chemokine CCL5 / metabolism,  secretion
Cytokines / metabolism*,  secretion
Granulocyte Colony-Stimulating Factor / genetics,  metabolism,  secretion
Interferon-beta / pharmacology
Interleukin-10 / metabolism,  secretion
Interleukin-6 / metabolism,  pharmacology,  secretion
Isoproterenol / pharmacology
Macrophages / cytology,  drug effects,  metabolism*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects,  physiology*
Sugar Acids / pharmacology
Time Factors
Transforming Growth Factor beta / pharmacology
Tumor Necrosis Factor-alpha / metabolism,  secretion
Grant Support
ID/Acronym/Agency:
GM 62114/GM/NIGMS NIH HHS; U54 GM062114/GM/NIGMS NIH HHS; U54 GM062114-089002/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL3; 0/Chemokine CCL5; 0/Cytokines; 0/Interleukin-6; 0/RNA, Messenger; 0/Sugar Acids; 0/Transforming Growth Factor beta; 0/Tumor Necrosis Factor-alpha; 1069-03-0/2-keto-3-deoxyoctonate; 130068-27-8/Interleukin-10; 143011-72-7/Granulocyte Colony-Stimulating Factor; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 77238-31-4/Interferon-beta; L628TT009W/Isoproterenol
Comments/Corrections

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