Linked Life Data

20043875

Source:http://linkedlifedata.com/resource/pubmed/id/20043875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-1-27
pubmed:abstractText
IgE-antigen-dependent crosslinking of the high affinity IgE receptor (FcepsilonRI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca(2+)) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls FcepsilonRI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed FcepsilonRI-dependent Ca(2+) mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca(2+) influx after FcepsilonRI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd(3+)) partially blocked FcepsilonRI-induced Ca(2+) influx in WT cells but, in contrast, completely inhibited Ca(2+) mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca(2+) channels (2-aminoethoxyphenyl-borane, 2-APB) blocked FcepsilonRI-induced maximal Ca(2+) rise in WT but not in Fyn -/- cells. Ca(2+) entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in FcepsilonRI-stimulated mast cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-aminoethoxydiphenyl borate, http://linkedlifedata.com/resource/pubmed/chemical/Boron Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgE, http://linkedlifedata.com/resource/pubmed/chemical/TRPC Cation Channels, http://linkedlifedata.com/resource/pubmed/chemical/TRPC3 cation channel, http://linkedlifedata.com/resource/pubmed/chemical/Trpc6 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Trpc7 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C beta
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
391
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1714-20
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Fyn kinase controls FcepsilonRI receptor-operated calcium entry necessary for full degranulation in mast cells.
pubmed:affiliation
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, Calzada de los Tenorios 235, Col Granjas Coapa, CP 14330 Mexico City, Mexico.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't