Gene interactions and pathways from curated databases and text-mining
Biochem Biophys Res Commun 2005, PMID: 15670770

TRAF-dependent association of protein kinase Tpl2/COT1 (MAP3K8) with CD40.

Chan, Henry; Reed, John C

Signaling by TNF-family receptor CD40 involves TRAF-family adaptor proteins, leading to activation of protein kinases that induce NFkappaB-family transcription factors. We report here that mitogen activated protein kinase kinase kinase-8 (MAP3K8), Tpl2/COT1, is recruited to the CD40 complex via a mechanism dependent on TRAF-binding sites in CD40. Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40-mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF. Tpl2 (-/-) fibroblasts were also deficient in CD40 but not TNF signaling, further supporting a unique role for Tpl2 in CD40 signaling. Experiments using dominant-negative Tpl2 suggest this kinase functions distal to TRAFs but proximal to the TAK1/TAB1 signaling complex, within the IKK/NFkappaB activation pathway. These results indicate a distinction between TNF Receptor family members CD40 and TNFR1 in their utilization of MAP3Ks, and demonstrate TRAF-dependence of Tpl2 association with the CD40 receptor complex.

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Text Mining Data

CD40 → TRAF: " TRAF dependent association of protein kinase Tpl2/COT1 ( MAP3K8 ) with CD40 "

Tpl2/COT1 → TRAF: " TRAF dependent association of protein kinase Tpl2/COT1 ( MAP3K8 ) with CD40 "

IkappaB kinase → CD40: " Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40 mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF "

NFkappaB-responsive → CD40: " Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40 mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF "

NFkappaB-responsive → IkappaB kinase: " Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40 mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF "

CD40 ⊣ Tpl2: " Tpl2 ( -/- ) fibroblasts were also deficient in CD40 but not TNF signaling, further supporting a unique role for Tpl2 in CD40 signaling "

Manually curated Databases

  • IRef Biogrid Interaction: TAB2 — MAP3K8 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MAP3K8 — CD40 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TRAF2 — MAP3K8 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MAP3K8 — TRAF6 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CHUK — NFKBIA (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: NFKBIA — IKBKG (direct interaction, enzymatic study)
  • IRef Hprd Interaction: CD40 — MAP3K8 (in vivo)
  • IRef Hprd Interaction: MAP3K8 — TRAF6 (in vitro)
In total, 6 gene pairs are associated to this article in curated databases