Linked Life Data

21262349

Source:http://linkedlifedata.com/resource/pubmed/id/21262349

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-2-28
pubmed:abstractText
B cells require signals transduced by the B cell antigen receptor (BCR) to provide humoral adaptive immunity. These signals are modulated by co-receptors like the Fc? receptor IIb (Fc?RIIb) that prevents activation of B cells after co-ligation with the BCR. Positive and negative effectors need to be precisely organized into signaling complexes, which requires adapter proteins like the growth factor receptor-bound protein 2 (Grb2). Here, we address the question how Grb2-mediated signal integration is affected by Fc?RIIb. Our data reveal that concomitant engagement of BCR and Fc?RIIb leads to markedly increased Grb2-mediated formation of ternary protein complexes comprising downstream of kinase-3 (Dok-3), Grb2, and the SH2 domain-containing inositol phosphatase (SHIP). Consistently, we found Grb2 to be required for full Fc?RIIb-mediated negative regulation. To investigate how Fc?RIIb influences the entire Grb2 interactions, we utilized quantitative mass spectrometry to make a differential interactome analysis. This approach revealed a shift of Grb2 interactions towards negative regulators like Dok-3, SHIP and SHP-2 and reduced binding to other proteins like CD19. Hence, we provide evidence that Grb2-mediated signal integration is a dynamic process that is important for the crosstalk between the BCR and its co-receptor Fc?RIIb.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1873-3913
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
893-900
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells.
pubmed:affiliation
Georg August University of Göttingen, Institute of Cellular and Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't