|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
24
|
|
pubmed:dateCreated |
2011-6-17
|
|
pubmed:abstractText |
The inhibitor of Bruton tyrosine kinase ? (IBtk?) is a negative regulator of the Bruton tyrosine kinase (Btk), which plays a major role in B-cell differentiation; however, the mechanisms of IBtk?-mediated regulation of Btk are unknown. Here we report that B-cell receptor (BCR) triggering caused serine-phosphorylation of IBtk? at protein kinase C consensus sites and dissociation from Btk. By liquid chromatography and mass-mass spectrometry and functional analysis, we identified IBtk?-S87 and -S90 as the critical amino acid residues that regulate the IBtk? binding affinity to Btk. Consistently, the mutants IBtk? carrying S87A and S90A mutations bound constitutively to Btk and down-regulated Ca(2+) fluxes and NF-?B activation on BCR triggering. Accordingly, spleen B cells from Ibtk?(-/-) mice showed an increased activation of Btk, as evaluated by Y551-phosphorylation and sustained Ca(2+) mobilization on BCR engagement. These findings identify a novel pathway of Btk regulation via protein kinase C phosphorylation of IBtk?.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
1528-0020
|
|
pubmed:author |
pubmed-author:BrittiDomenicoD,
pubmed-author:De LaurentiisAnnamariaA,
pubmed-author:Di NapoliDanieleD,
pubmed-author:Di SalleEmanuelaE,
pubmed-author:FalconeCristinaC,
pubmed-author:FiumeGiuseppeG,
pubmed-author:GaspariMarcoM,
pubmed-author:GrecoAdelaideA,
pubmed-author:IaccinoEnricoE,
pubmed-author:JandaElzbietaE,
pubmed-author:LavecchiaLucaL,
pubmed-author:NevoloMariaM,
pubmed-author:PalmieriCamilloC,
pubmed-author:PisanoAntonioA,
pubmed-author:PontorieroMarilenaM,
pubmed-author:QuintoIleanaI,
pubmed-author:RossiAnnalisaA,
pubmed-author:ScalaGiuseppeG,
pubmed-author:VerheijElwinE
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
16
|
|
pubmed:volume |
117
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
6520-31
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:21482705-Alanine,
pubmed-meshheading:21482705-Amino Acid Substitution,
pubmed-meshheading:21482705-Animals,
pubmed-meshheading:21482705-Carrier Proteins,
pubmed-meshheading:21482705-Cells,
pubmed-meshheading:21482705-Cells, Cultured,
pubmed-meshheading:21482705-Humans,
pubmed-meshheading:21482705-Mice,
pubmed-meshheading:21482705-Mice, Knockout,
pubmed-meshheading:21482705-Mutation, Missense,
pubmed-meshheading:21482705-Phosphorylation,
pubmed-meshheading:21482705-Protein Kinase C,
pubmed-meshheading:21482705-Protein-Tyrosine Kinases,
pubmed-meshheading:21482705-Serine,
pubmed-meshheading:21482705-Signal Transduction
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Btk regulation in human and mouse B cells via protein kinase C phosphorylation of IBtk?.
|
|
pubmed:affiliation |
Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Catanzaro, Italy.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
