PMID- 9379019
OWN - NLM
STAT- MEDLINE
DCOM- 19971112
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 9
DP  - 1997 Nov 1
TI  - CD40-mediated signals inhibit the binding of TNF receptor-associated factor 2 to 
      the CD40 cytoplasmic domain.
PG  - 4244-51
AB  - TNF receptor-associated factor 2 (TRAF2) is a signal-transducing protein 
      associated with the CD40 cytoplasmic domain. It has been hypothesized that during 
      signal transduction, TRAF2 must be released from CD40 in order for it to interact 
      with downstream signaling molecules. We found that CD40 and TRAF2 were 
      constitutively associated with each other in a human B cell line. Following 
      stimulation with an anti-CD40 Ab, a decrease in the amount of CD40-associated 
      TRAF2 was observed that could not be explained by a change in total level of 
      either of the proteins. These results, as well as similar findings obtained with 
      293 cells overexpressing CD40 and TRAF2, suggested that CD40-mediated signals 
      inhibited the CD40-TRAF2 interaction. We then conducted binding studies using 
      CD40 cytoplasmic domain fusion proteins and TRAF2 derived from either control or 
      CD40-stimulated cell lines. These in vitro studies also indicated that the 
      binding of TRAF2 to the CD40 cytoplasmic domain was inhibited by CD40 
      stimulation. The results of these experiments, as well as differences between the 
      in vitro and in vivo findings, indicated that multiple mechanisms were involved 
      in the inhibition of the CD40-TRAF2 interaction by CD40 signals. Possible 
      mechanisms of inhibition are discussed based on mapping of the TRAF2 binding site 
      on the CD40 cytoplasmic domain.
FAU - Chaudhuri, A
AU  - Chaudhuri A
AD  - Mucosal Immunology Laboratory, Combined Program in Pediatric Gastroenterology and 
      Nutrition, Massachusetts General Hospital, Charlestown 02129, USA.
FAU - Orme, S
AU  - Orme S
FAU - Eilam, S
AU  - Eilam S
FAU - Cherayil, B J
AU  - Cherayil BJ
LA  - eng
GR  - T-32-DK-07477/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD40 Antigens)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
SB  - IM
MH  - B-Lymphocytes/*immunology/metabolism
MH  - Binding Sites/immunology
MH  - CD40 Antigens/*immunology
MH  - Cell Line
MH  - Humans
MH  - Proteins/*immunology
MH  - Signal Transduction/*immunology
MH  - TNF Receptor-Associated Factor 2
EDAT- 1997/10/31 00:00
MHDA- 1997/10/31 00:01
CRDT- 1997/10/31 00:00
PHST- 1997/10/31 00:00 [pubmed]
PHST- 1997/10/31 00:01 [medline]
PHST- 1997/10/31 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Nov 1;159(9):4244-51.