Linked Life Data

10601993

Source:http://linkedlifedata.com/resource/pubmed/id/10601993

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-1-4
pubmed:abstractText
CD40, a member of the tumor necrosis factor receptor (TNF-R) superfamily, is expressed on the surface of B cells, where its engagement results in IL-6 secretion. In this study, we characterize the specific molecular requirements for CD40-mediated IL-6 production. Engagement of CD40 on either a B cell line or normal mouse splenic B cells with a membrane-bound form of CD154 (also known as CD40L or gp39) induced IL-6 secretion as well as up-regulation of IL-6 mRNA, but cross-linking CD40 with agonistic anti-CD40 mAb did not, although these mAb induce many other CD40 activation events, including the nuclear translocation of the transcription factor NF-kappaB. Using a mouse B cell line stably transfected with various human CD40 (hCD40) cytoplasmic truncation and point mutants, we show that the region from amino acids 202 to 225 in the cytoplasmic domain of CD40 is necessary for IL-6 secretion. However, the carboxy-terminal 32 amino acids are not, although these residues are required for CD40-mediated NF-kappaB activation. In addition, CD40 mutants previously shown to lack binding to TRAF2 and -3 are fully capable of inducing IL-6 production. Thus, CD40-mediated IL-6 induction is independent of NF-kappaB activation and the binding of TRAF2 and -3, but CD40 must be engaged by trimeric CD154 on cell membranes to activate production of IL-6.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3855-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Membrane-bound CD154, but not CD40-specific antibody, mediates NF-kappaB-independent IL-6 production in B cells.
pubmed:affiliation
Department of Microbiology University of Iowa, Iowa City 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.