PMID- 9366415
OWN - NLM
STAT- MEDLINE
DCOM- 19971125
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 10
DP  - 1997 Nov 15
TI  - Characterization of CD40 signaling determinants regulating nuclear factor-kappa B 
      activation in B lymphocytes.
PG  - 4898-906
AB  - CD40 signaling to B cells is important for generating an effective humoral immune 
      response. CD40 ligation leads to B cell activation events such as proliferation, 
      Ig secretion, isotype switching, and up-regulation of cell surface molecules, as 
      well as the generation of memory B cells. Many of these events are dependent upon 
      the ability of CD40 to activate the transcription factor NF-kappa B (NF-kappa B). 
      To define the CD40 signaling components upstream of NF-kappa B activation and the 
      functional consequences downstream of NF-kappa B activation, we examined mouse B 
      cell transfectants expressing wild-type or mutant human CD40. Analysis of CD40 
      cytoplasmic domain truncation and point mutants defined a 10-amino acid CD40 
      cytoplasmic signaling determinant required for NF-kappa B activation. A threonine 
      residue at position 234, previously shown to be important for CD40 association 
      with TNF receptor-associated factor 2 (TRAF2), TRAF3, and TRAF5, was not required 
      for NF-kappa B activation. This suggests that in B cells, CD40-induced NF-kappa B 
      activation can occur independently of TRAF2 and TRAF5 association. NF-kappa B 
      activation was independent of the transmembrane domain of CD40, suggesting that 
      it is independent of p23, a molecule that associates with CD40 in a region other 
      than the cytoplasmic domain. Proteasome-dependent inhibitory kappa B alpha (I 
      kappa B alpha) and I kappa B beta degradation occurred downstream of CD40 
      ligation and preceded CD40-mediated NF-kappa B nuclear translocation. CD40- or 
      pervanadate-mediated I kappa B tyrosine phosphorylation was not detected. 
      NF-kappa B activation correlated with the ability of CD40 to induce Ab secretion 
      and the up-regulation of ICAM-1 and LFA-1. However, NF-kappa B activation was 
      insufficient for CD40-mediated up-regulation of B7-1, Fas, and CD23.
FAU - Hsing, Y
AU  - Hsing Y
AD  - The Immunology Graduate Program, University of Iowa, Iowa City 52242, USA.
FAU - Hostager, B S
AU  - Hostager BS
FAU - Bishop, G A
AU  - Bishop GA
LA  - eng
GR  - AI28847/AI/NIAID NIH HHS/United States
GR  - CA66570/CA/NCI NIH HHS/United States
GR  - DK25295/DK/NIDDK NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
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 (Epitopes, B-Lymphocyte)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 0 (RELB protein, human)
RN  - 0 (Relb protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 147337-75-5 (Transcription Factor RelB)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - B-Lymphocytes/*immunology/metabolism
MH  - Biological Transport/drug effects
MH  - CD40 Antigens/*chemistry/genetics/*physiology
MH  - Cytoplasm/chemistry/immunology/physiology
MH  - Epitopes, B-Lymphocyte/*chemistry/physiology
MH  - Humans
MH  - Lymphoma, B-Cell
MH  - Mice
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism/physiology
MH  - NF-kappa B p50 Subunit
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-rel
MH  - Signal Transduction/*immunology
MH  - Structure-Activity Relationship
MH  - Transcription Factor RelB
MH  - *Transcription Factors
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1997/11/20 00:00
MHDA- 1997/11/20 00:01
CRDT- 1997/11/20 00:00
PHST- 1997/11/20 00:00 [pubmed]
PHST- 1997/11/20 00:01 [medline]
PHST- 1997/11/20 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Nov 15;159(10):4898-906.