Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2001, PMID: 11244088

The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor.

Wooten, M W; Seibenhener, M L; Mamidipudi, V; Diaz-Meco, M T; Barker, P A; Moscat, J

Nerve growth factor (NGF) binding to both p75 and TrkA neurotrophin receptors activates the transcription factor nuclear factor kappaB (NF-kappaB). Here we show that the atypical protein kinase C-interacting protein, p62, which binds TRAF6, selectively interacts with TrkA but not p75. In contrast, TRAF6 interacts with p75 but not TrkA. We demonstrate the formation of a TRAF6-p62 complex that serves as a bridge linking both p75 and TrkA signaling. Of functional relevance, transfection of antisense p62-enhanced p75-mediated cell death and diminished NGF-induced differentiation occur through a mechanism involving inhibition of IKK activity. These findings reveal a new function for p62 as a common platform for communication of both p75-TRAF6 and TrkA signals. Moreover, we demonstrated that p62 serves as a scaffold for activation of the NF-kappaB pathway, which mediates NGF survival and differentiation responses.

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Text Mining Data

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Manually curated Databases

  • OpenBEL Selventa BEL large corpus: O/k complex () → Complex of SQSTM1-TRAF6 (increases, SQSTM1/TRAF6 Activity)
    Evidence: we demonstrated that p62 serves as a scaffold for activation of the NF-kappaB pathway, which mediates NGF survival and differentiation responses.
  • IRef Biogrid Interaction: SQSTM1 — NTRK1 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: SQSTM1 — NTRK1 (in vivo)
  • IRef Hprd Interaction: SQSTM1 — TRAF6 (in vivo)
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/TRKA complex (NTRK1-NGF) → NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs complex (NGF-NGFR-TRAF6-RIPK2-IRAK1-SQSTM1-PRKCI_PRKCZ) (modification, inhibits)
    Evidence: mutant phenotype, reporter gene, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/TRKA complex (NTRK1-NGF) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, inhibits)
    Evidence: mutant phenotype, reporter gene, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs complex (NGF-NGFR-TRAF6-RIPK2-IRAK1-SQSTM1-PRKCI_PRKCZ) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
    Evidence: mutant phenotype, reporter gene, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK complex (NGF-NGFR-TRAF6-RIPK2-IRAK1) → Atypical PKCs (PRKCI/PRKCZ) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK complex (NGF-NGFR-TRAF6-RIPK2-IRAK1) → p62 (SQSTM1) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK complex (NGF-NGFR-TRAF6-RIPK2-IRAK1) → NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs complex (NGF-NGFR-TRAF6-RIPK2-IRAK1-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: Atypical PKCs (PRKCI/PRKCZ) → p62 (SQSTM1) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: Atypical PKCs (PRKCI/PRKCZ) → NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs complex (NGF-NGFR-TRAF6-RIPK2-IRAK1-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: p62 (SQSTM1) → NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs complex (NGF-NGFR-TRAF6-RIPK2-IRAK1-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: NGF (dimer)/TRKA complex (NTRK1-NGF) → Atypical PKCs (PRKCI/PRKCZ) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: NGF (dimer)/TRKA complex (NTRK1-NGF) → p62 (SQSTM1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: NGF (dimer)/TRKA complex (NTRK1-NGF) → NGF (dimer)/TRKA/p62/Atypical PKCs complex (NTRK1-NGF-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: Atypical PKCs (PRKCI/PRKCZ) → p62 (SQSTM1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: Atypical PKCs (PRKCI/PRKCZ) → NGF (dimer)/TRKA/p62/Atypical PKCs complex (NTRK1-NGF-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: p62 (SQSTM1) → NGF (dimer)/TRKA/p62/Atypical PKCs complex (NTRK1-NGF-SQSTM1-PRKCI_PRKCZ) (modification, collaborate)
    Evidence: physical interaction
  • Reactome Reaction: PRKCI → NGFR (indirect_complex)
  • Reactome Reaction: TRAF6 → IRAK1 (direct_complex)
  • Reactome Reaction: PRKCI → SQSTM1 (reaction)
  • Reactome Reaction: NGF → TRAF6 (indirect_complex)
  • Reactome Reaction: NGF → SQSTM1 (indirect_complex)
  • Reactome Reaction: PRKCI → TRAF6 (direct_complex)
  • Reactome Reaction: SQSTM1 → IRAK1 (direct_complex)
  • Reactome Reaction: PRKCI → IRAK1 (reaction)
  • Reactome Reaction: PRKCI → NGF (reaction)
  • Reactome Reaction: NGFR → SQSTM1 (indirect_complex)
  • Reactome Reaction: NGFR → SQSTM1 (reaction)
  • Reactome Reaction: NGFR → IRAK1 (indirect_complex)
  • Reactome Reaction: TRAF6 → SQSTM1 (reaction)
  • Reactome Reaction: TRAF6 → SQSTM1 (direct_complex)
  • Reactome Reaction: NGFR → TRAF6 (indirect_complex)
  • Reactome Reaction: NGF → SQSTM1 (reaction)
  • Reactome Reaction: PRKCI → NGFR (reaction)
  • Reactome Reaction: PRKCI → NGF (indirect_complex)
  • Reactome Reaction: PRKCI → SQSTM1 (direct_complex)
  • Reactome Reaction: NGF → IRAK1 (indirect_complex)
  • Reactome Reaction: PRKCI → IRAK1 (direct_complex)
  • Reactome Reaction: PRKCI → TRAF6 (reaction)
  • Reactome Reaction: SQSTM1 → IRAK1 (reaction)
In total, 75 gene pairs are associated to this article in curated databases