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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Pharmacol Ther. 2020 Oct 20;219:107709. doi: 10.1016/j.pharmthera.2020.107709

Table 1.

CD40/CD40L signal pathways in cellular immune response

Cell Signal pathway PMID
B cell TRAF2↑ → canonical NF-κB (p65:p65)↑ & noncanonical NF-κB (p52:Rc1B)↓ → cell proliferation & activation↑ 15539150
B cell TRAF2↑ → MEKK1↑ → JNK & p38↑ → AP1↑ → cell proliferation & Ab production↑ 17143273
B cell TRAF6↑ → JNK & p38↑ → cell proliferation, activation & Ab isotype switching↑ 12354380
WEHI 231 B cell TRAF3↑ → PI3K↑ → NADPH oxidase↑ → ROS production↑ 14688330
A20 B cell TRAF6↑ → PI3K↑ → AKT↑ → apoptosis↓ 12637493
B cell JAK3↑ → STAT3↑ → CD23, ICAM-1 & lymphotoxin-α↑ 9133417
DC TRAF2 & 3↑ → Lyn↑ → ERK1/2↑ → IL-1α/β & IL-1Ra↑
TRAF2 & 3↑ → Lyn↑ → p38↑ → IL12p40↑
TRAF2 & 3↑ → p38↑ → IL12p40↑
10880443
MC/MΦ TRAF6↑ → Src↑ → ERK1/2↑ → TNF-α IL-6 & IL-1β↑ 15634933
MC JAK3↑ → STAT5↑ 10395671
Endothelial cell TRAF6↑ → c-Cb1↑ → PI3K↑ → AKT ↑ → proliferation, motility, angiogenesis↑ & apoptosis↓ 12637493
Lung fibroblast TRAF6↑ → canonical NF-κB (p65) & JNK↑ → IL-8 & IL-6↑ 16143987
Airway epithelial cell TRAF3↑ → canonical NF-κB (p65:p65)↑ → RANTES↑ 12122011
293T cell TRAF6↑ → canonical NF-κB (p50:p65)↑
TRAF2 & 5↑ → canonical NF-κB (p50:p65)↑
TRAF2 & 5 noncanonical NF-κB (p52:RelB)↑
15708970
293T cell Cytoplasmic tail-N → TRAF2, 3 & 5 ↑; Cytoplasmic tail-C → TRAF6 ↑ 9990007
Spodoptera frugiperda (Sf21) cell PVQET sequence of CD40 cytoplasmic domain → TRAF1, 2 & 3↑
QEPQEINF sequence of CD40 cytoplasmic domain → TRAF6↑
9718306
HEK 293 cell Affinity to trimeric CD40: trimeric TRAF2 > TRAF3 >> TRAF1 & 6 10433725
HEK 293 cell Affinity to CD40: TRAF2 & 3 > TRAF5 & 6 9990039
HEK 293 cell TRAF6↑ → Ras↑ → Raf↑ → MEKl↑ → ERK1/2↑; TRAF6↑ → ERK1/2↑ 9432981
Malignant urothelial cell TRAF3↑ → JNK↑ → APl↑ → caspase-9↑ → caspase-3↑ → apoptosis ↑ 16429118

Abbreviations: Ab, antibody; AKT, protein kinase B; AP1, activator protein 1; CD40L, CD40 ligand; DC, dendritic cell; ERK1/2, extracellular signal-regulated kinases 1/2; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; JAK3, janus kinase 3; JNK, c-Jun N-terminal kinase; Lyn, LYN proto-oncogene, Src family tyrosine kinase; MC, monocyte; MΦ, macrophage; MEK1, MAPK/ERK kinasel; MEKK1, MAPK kinase kinase 1; NF-κΒ, nuclear factor kappa-B; PI3K, phosphoinositide-3-kinase; RANTES, regulated upon activation normal T cell expressed and secreted factor; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TNF-α, tumor necrosis factor-α; TRAF, tumor necrosis factor receptor-associated factor.