Document Detail


Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis.
MedLine Citation:
PMID:  19700408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane. During phagocytosis, Ras density was similar on the surface and invaginating areas of the membrane, but activation was detectable only in the latter and in sealed phagosomes. Ras activation was associated with the recruitment of RasGRP3, a diacylglycerol-dependent Ras/Rap1 exchange factor. Recruitment to phagosomes of RasGRP3, which contains a C1 domain, parallels and appears to be due to the formation of diacylglycerol. Accordingly, Ras and Rap1 activation was precluded by antagonists of phospholipase C and of diacylglycerol binding. Ras is dispensable for phagocytosis but controls activation of extracellular signal-regulated kinase, which is partially impeded by diacylglycerol inhibitors. By contrast, cross-activation of complement receptors by stimulation of Fcgamma receptors requires Rap1 and involves diacylglycerol. We suggest a role for diacylglycerol-dependent exchange factors in the activation of Ras and Rap1, which govern distinct processes induced by Fcgamma receptor-mediated phagocytosis to enhance the innate immune response.
Authors:
Roberto J Botelho; Rene E Harrison; James C Stone; John F Hancock; Mark R Philips; Jenny Jongstra-Bilen; David Mason; Jonathan Plumb; Michael R Gold; Sergio Grinstein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-08-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-12     Completed Date:  2009-11-24     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28522-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Diglycerides / metabolism*
Erythrocytes / metabolism
Immunity, Innate
Immunoglobulin G / metabolism
Mice
Microscopy, Confocal / methods
Phagocytosis
Protein Isoforms
Protein Structure, Tertiary
Reverse Transcriptase Polymerase Chain Reaction
Sheep
Signal Transduction
rap1 GTP-Binding Proteins / metabolism*
ras Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
CA116034/CA/NCI NIH HHS; GM55279/GM/NIGMS NIH HHS; R01 GM066717/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Diglycerides; 0/Immunoglobulin G; 0/Protein Isoforms; EC 3.6.5.2/rap1 GTP-Binding Proteins; EC 3.6.5.2/ras Proteins
Comments/Corrections

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