Linked Life Data

16316995

Source:http://linkedlifedata.com/resource/pubmed/id/16316995

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-1-30
pubmed:abstractText
Engagement of the high affinity receptor for IgE (FcepsilonRI) on mast cells results in the production and secretion of sphingosine 1-phosphate (S1P), a lipid metabolite present in the lungs of allergen-challenged asthmatics. Herein we report that two isoforms of sphingosine kinase (SphK1 and SphK2) are expressed and activated upon FcepsilonRI engagement of bone marrow-derived mast cells (BMMC). Fyn kinase is required for FcepsilonRI coupling to SphK1 and -2 and for subsequent S1P production. Normal activation of SphK1 and -2 was restored by expression of wild type Fyn but only partly with a kinase-defective Fyn, indicating that induction of SphK1 and SphK2 depended on both catalytic and noncatalytic properties of Fyn. Downstream of Fyn, the requirements for SphK1 activation differed from that of SphK2. Whereas SphK1 was considerably dependent on the adapter Grb2-associated binder 2 and phosphatidylinositol 3-OH kinase, SphK2 showed minimal dependence on these molecules. Fyn-deficient BMMC were defective in chemotaxis and, as previously reported, in degranulation. These functional responses were partly reconstituted by the addition of exogenous S1P to FcepsilonRI-stimulated cells. Taken together with our previous study, which demonstrated delayed SphK activation in Lyn-deficient BMMC, we propose a cooperative role between Fyn and Lyn kinases in the activation of SphKs, which contributes to mast cell responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin E, http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., 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/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/lyn protein-tyrosine kinase, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine kinase, http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2515-25
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses.
pubmed:affiliation
Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural