PMID- 10202013
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 8
DP  - 1999 Apr 15
TI  - An 11-amino acid sequence in the cytoplasmic domain of CD40 is sufficient for 
      activation of c-Jun N-terminal kinase, activation of MAPKAP kinase-2, 
      phosphorylation of I kappa B alpha, and protection of WEHI-231 cells from 
      anti-IgM-induced growth arrest.
PG  - 4720-30
AB  - We have previously shown that CD40 causes strong activation of the c-Jun 
      N-terminal kinase (JNK), the p38 mitogen-activated protein kinases (MAPK) and 
      MAPKAP kinase-2, a downstream target of p38 MAPK. To identify signaling motifs in 
      the CD40 cytoplasmic domain that are responsible for activation of these kinases, 
      we have created a set of 11 chimeric receptors consisting of the extracellular 
      and transmembrane domains of CD8 fused to portions of the murine CD40 cytoplasmic 
      domain. These chimeric receptors were expressed in WEHI-231 B lymphoma cells. We 
      found that amino acids 35-45 of the CD40 cytoplasmic domain constitute an 
      independent signaling motif that is sufficient for activation of the JNK and p38 
      MAPK pathways, as well as for induction of I kappa B alpha phosphorylation and 
      degradation. Amino acids 35-45 were also sufficient to protect WEHI-231 cells 
      from anti-IgM-induced growth arrest. This is the same region of CD40 required for 
      binding the TNF receptor-associated factor-2 (TRAF2), TRAF3, and TRAF5 adapter 
      proteins. These data support the idea that one or more of these TRAF proteins 
      couple CD40 to the kinase cascades that activate NF-kappa B, JNK, and p38 MAPK.
FAU - Sutherland, C L
AU  - Sutherland CL
AD  - Department of Microbiology and Immunology, University of British Columbia, 
      Vancouver, Canada.
FAU - Krebs, D L
AU  - Krebs DL
FAU - Gold, M R
AU  - Gold MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (CD40 Antigens)
RN  - 0 (CD8 Antigens)
RN  - 0 (CD8 receptor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (anti-IgM)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Anti-Idiotypic/*physiology
MH  - Base Sequence
MH  - Binding Sites/immunology
MH  - CD40 Antigens/genetics/*physiology
MH  - CD8 Antigens/genetics
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Division/immunology
MH  - Cytoplasm/chemistry/enzymology/*immunology
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation/immunology
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Immunoglobulin M/*immunology
MH  - Intracellular Signaling Peptides and Proteins
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Peptide Fragments/physiology
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proteins/metabolism
MH  - Receptors, Antigen, T-Cell/biosynthesis/genetics
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Recombinant Fusion Proteins/biosynthesis/immunology
MH  - Signal Transduction/immunology
MH  - TNF Receptor-Associated Factor 6
MH  - Threonine/physiology
MH  - Tumor Cells, Cultured
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Apr 15;162(8):4720-30.