J Biol Chem 2001,
PMID: 11244088
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
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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