◀ Back to IL6
IL6 — IL6R
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
Complex of IGF1R-IL6R
→
IL6
(increases)
Ishikawa et al., J Clin Exp Hematop 2006*
Evidence: Accordingly, under the cellular context of the elevated expression of IL- 6Ra on myeloma cells, it is assumed that IL-6Ra molecules are located close to IGF-I receptors at lipid rafts, and IL-6 stimulation triggers the complex formation of IL-6Ra not only with gp130 but also with IGF-I receptors, leading to autophosphorylation of IGF-I receptor b and subsequent acti- vation of PI-3 kinase-Akt pathways (Fig. 4) 79 .
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BioCarta il 6 signaling pathway:
IL-6 (IL6)
→
IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6R-LRPPRC)
(modification, collaborate)
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BioCarta il 6 signaling pathway:
IL-6 (IL6)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta il 6 signaling pathway:
IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6R-LRPPRC)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
ERBB2
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6-IL6R-LRPPRC-ERBB2)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
ERBB2
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6-IL6R-LRPPRC-ERBB2)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6 (IL6)
→
IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6R-LRPPRC-ERBB2)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6 (IL6)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6-IL6R-LRPPRC-ERBB2)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6R-LRPPRC-ERBB2)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/ERBB2 complex (IL6-IL6R-LRPPRC-ERBB2)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKs complex (IL6-IL6R-LRPPRC-JAK2_JAK1_JAK3)
→
STAT3
(modification, activates)
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BioCarta il 6 signaling pathway:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKS complex (JAK2_JAK1_JAK3-LRPPRC-IL6R-IL6)
→
STAT3
(modification, activates)
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BioCarta il 6 signaling pathway:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKS complex (JAK2_JAK1_JAK3-LRPPRC-IL6R-IL6)
→
JAKs (JAK2/JAK1/JAK3)
(modification, collaborate)
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BioCarta il 6 signaling pathway:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKS complex (JAK2_JAK1_JAK3-LRPPRC-IL6R-IL6)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta il 6 signaling pathway:
JAKs (JAK2/JAK1/JAK3)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
JAKs (JAK2/JAK1/JAK3)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
JAKs (JAK2/JAK1/JAK3)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKs complex (IL6-IL6R-LRPPRC-JAK2_JAK1_JAK3)
(modification, collaborate)
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BioCarta role of erbb2 in signal transduction and oncology:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130 complex (IL6-IL6R-LRPPRC)
→
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKs complex (IL6-IL6R-LRPPRC-JAK2_JAK1_JAK3)
(modification, collaborate)
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BioCarta il 6 signaling pathway:
IL-6/IL-6/IL-6R-alpha/IL-6R-alpha/GP130/GP130/JAKS complex (JAK2_JAK1_JAK3-LRPPRC-IL6R-IL6)
→
SHC/GRB2/SOS-1 complex (SOS1-GRB2-SHC1)
(modification, activates)
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KEGG Cytokine-cytokine receptor interaction:
IL6
→
Complex of IL6R-IL6ST
(protein-protein, activation)
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NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
SHP2 (PTPN11)
(modification, activates)
Lang et al., Nat Immunol 2003, Schaper et al., Biochem J 1998
Evidence: mutant phenotype, physical interaction, other species
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NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, activates)
Lang et al., Nat Immunol 2003, Schaper et al., Biochem J 1998
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
SOCS3 (SOCS3)
(modification, collaborate)
Schmitz et al., J Biol Chem 2000
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, collaborate)
Schmitz et al., J Biol Chem 2000
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
SOCS3 (SOCS3)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, collaborate)
Schmitz et al., J Biol Chem 2000
Evidence: physical interaction
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NCI Pathway Database IL6-mediated signaling events:
IL6 (IL6)
→
IL6/IL6RA complex (IL6-IL6R)
(modification, collaborate)
Boulanger et al., Science 2003, Taga et al., Cell 1989, Yamasaki et al., Science 1988*
Evidence: physical interaction
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NCI Pathway Database IL6-mediated signaling events:
IL6 (IL6)
→
IL6RA (IL6R)
(modification, collaborate)
Boulanger et al., Science 2003, Taga et al., Cell 1989, Yamasaki et al., Science 1988*
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA complex (IL6-IL6R)
→
IL6RA (IL6R)
(modification, collaborate)
Boulanger et al., Science 2003, Taga et al., Cell 1989, Yamasaki et al., Science 1988*
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT3 (dimer ) complex (STAT3)
(modification, activates)
Sonnenblick et al., Mol Cell Biol 2004, Chung et al., Science 1997
Evidence: mutant phenotype, reporter gene, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
MITF (MITF)
(modification, activates)
Sonnenblick et al., Mol Cell Biol 2004, Chung et al., Science 1997
Evidence: mutant phenotype, reporter gene, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT3 (dimer)/PIAS3 complex (STAT3-PIAS3)
(modification, activates)
Sonnenblick et al., Mol Cell Biol 2004, Chung et al., Science 1997
Evidence: mutant phenotype, reporter gene, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
PIAS3/MITF complex (PIAS3-MITF)
(modification, activates)
Sonnenblick et al., Mol Cell Biol 2004, Chung et al., Science 1997
Evidence: mutant phenotype, reporter gene, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
PTPEC (PTPRE)
→
IL6/IL6RA complex (IL6-IL6R)
(modification, inhibits)
Tanuma et al., J Biol Chem 2000, Boulanger et al., Science 2003, Hibi et al., Cell 1990, Taga et al., Cell 1989, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
PTPEC (PTPRE)
→
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4 complex (IL6-IL6R-IL6ST-TYK2-LMO4)
(modification, inhibits)
Tanuma et al., J Biol Chem 2000, Boulanger et al., Science 2003, Hibi et al., Cell 1990, Taga et al., Cell 1989, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA complex (IL6-IL6R)
→
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4 complex (IL6-IL6R-IL6ST-TYK2-LMO4)
(modification, collaborate)
Tanuma et al., J Biol Chem 2000, Boulanger et al., Science 2003, Hibi et al., Cell 1990, Taga et al., Cell 1989, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA complex (IL6-IL6R)
→
gp130 (dimer)/TYK2/TYK2/LMO4 complex (TYK2-IL6ST-LMO4)
(modification, collaborate)
Tanuma et al., J Biol Chem 2000, Boulanger et al., Science 2003, Hibi et al., Cell 1990, Taga et al., Cell 1989, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4 complex (IL6-IL6R-IL6ST-TYK2-LMO4)
→
gp130 (dimer)/TYK2/TYK2/LMO4 complex (TYK2-IL6ST-LMO4)
(modification, collaborate)
Tanuma et al., J Biol Chem 2000, Boulanger et al., Science 2003, Hibi et al., Cell 1990, Taga et al., Cell 1989, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
GRB2/SOS1/GAB family complex (GRB2-SOS1-GAB1_GAB2)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/Hck complex (IL6-IL6R-IL6ST-JAK1-LMO4-HCK)
(modification, collaborate)
Kim et al., Mol Cell Biol 1999, Podar et al., J Biol Chem 2004
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
SHP2 (PTPN11)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/Hck complex (IL6-IL6R-IL6ST-JAK1-LMO4-HCK)
(modification, collaborate)
Kim et al., Mol Cell Biol 1999, Podar et al., J Biol Chem 2004
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1 (STAT1)
(modification, activates)
Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Gerhartz et al., J Biol Chem 1996
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, activates)
Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Gerhartz et al., J Biol Chem 1996
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT3 (dimer ) complex (STAT3)
(modification, activates)
Kortylewski et al., J Biol Chem 2003
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
FOXO1 (FOXO1)
(modification, activates)
Kortylewski et al., J Biol Chem 2003
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT3 (dimer)/FOXO1 complex (STAT3-FOXO1)
(modification, activates)
Kortylewski et al., J Biol Chem 2003
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4 complex (IL6-IL6R-IL6ST-JAK2-LMO4)
→
IL6/IL6RA complex (IL6-IL6R)
(modification, collaborate)
Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Hibi et al., Cell 1990, Taga et al., Cell 1989, Narazaki et al., Proc Natl Acad Sci U S A 1994, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4 complex (IL6-IL6R-IL6ST-JAK2-LMO4)
→
gp130 (dimer)/JAK2/JAK2/LMO4 complex (JAK2-IL6ST-LMO4)
(modification, collaborate)
Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Hibi et al., Cell 1990, Taga et al., Cell 1989, Narazaki et al., Proc Natl Acad Sci U S A 1994, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA complex (IL6-IL6R)
→
gp130 (dimer)/JAK2/JAK2/LMO4 complex (JAK2-IL6ST-LMO4)
(modification, collaborate)
Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Hibi et al., Cell 1990, Taga et al., Cell 1989, Narazaki et al., Proc Natl Acad Sci U S A 1994, Lütticken et al., Science 1994, Stahl et al., Science 1994
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
PIAS1 (PIAS1)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
(modification, collaborate)
Liu et al., Proc Natl Acad Sci U S A 1998
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1 (STAT1)
(modification, activates)
Liu et al., Proc Natl Acad Sci U S A 1998
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT1/PIAS1 complex (STAT1-PIAS1)
(modification, activates)
Liu et al., Proc Natl Acad Sci U S A 1998
Evidence: physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
MKK6 (MAP2K6)
(modification, activates)
Bode et al., Biol Chem 2001
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
VAV1 (VAV1)
(modification, activates)
Schuringa et al., Biochem J 2000
-
NCI Pathway Database SHP2 signaling:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
SHP2 (PTPN11)
(modification, activates)
Schaper et al., Biochem J 1998
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
gp130 (dimer)/JAK1/JAK1/LMO4 complex (JAK1-IL6ST-LMO4)
→
IL6/IL6RA complex (IL6-IL6R)
(modification, collaborate)
Kurth et al., J Immunol 2000, Tanuma et al., J Biol Chem 2000, Pflanz et al., J Immunol 2000, Chow et al., Science 2001, Haan et al., J Biol Chem 2001, Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Schroers et al., Protein Sci 2005, Giese et al., J Cell Sci 2005, Murakami et al., Proc Natl Acad Sci U S A 1991, Tenhumberg et al., Biochem Biophys Res Commun 2006, Hibi et al., Cell 1990, Taga et al., Cell 1989, Guschin et al., EMBO J 1995, Horsten et al., FEBS Lett 1995, Ward et al., J Biol Chem 1994, Lütticken et al., Science 1994, Yawata et al., EMBO J 1993, Murakami et al., Science 1993, Horsten et al., J Biol Chem 1997, Rodig et al., Cell 1998, Kurth et al., J Immunol 1999
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
gp130 (dimer)/JAK1/JAK1/LMO4 complex (JAK1-IL6ST-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
(modification, collaborate)
Kurth et al., J Immunol 2000, Tanuma et al., J Biol Chem 2000, Pflanz et al., J Immunol 2000, Chow et al., Science 2001, Haan et al., J Biol Chem 2001, Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Schroers et al., Protein Sci 2005, Giese et al., J Cell Sci 2005, Murakami et al., Proc Natl Acad Sci U S A 1991, Tenhumberg et al., Biochem Biophys Res Commun 2006, Hibi et al., Cell 1990, Taga et al., Cell 1989, Guschin et al., EMBO J 1995, Horsten et al., FEBS Lett 1995, Ward et al., J Biol Chem 1994, Lütticken et al., Science 1994, Yawata et al., EMBO J 1993, Murakami et al., Science 1993, Horsten et al., J Biol Chem 1997, Rodig et al., Cell 1998, Kurth et al., J Immunol 1999
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
PTPEC (PTPRE)
→
IL6/IL6RA complex (IL6-IL6R)
(modification, inhibits)
Kurth et al., J Immunol 2000, Tanuma et al., J Biol Chem 2000, Pflanz et al., J Immunol 2000, Chow et al., Science 2001, Haan et al., J Biol Chem 2001, Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Schroers et al., Protein Sci 2005, Giese et al., J Cell Sci 2005, Murakami et al., Proc Natl Acad Sci U S A 1991, Tenhumberg et al., Biochem Biophys Res Commun 2006, Hibi et al., Cell 1990, Taga et al., Cell 1989, Guschin et al., EMBO J 1995, Horsten et al., FEBS Lett 1995, Ward et al., J Biol Chem 1994, Lütticken et al., Science 1994, Yawata et al., EMBO J 1993, Murakami et al., Science 1993, Horsten et al., J Biol Chem 1997, Rodig et al., Cell 1998, Kurth et al., J Immunol 1999
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
PTPEC (PTPRE)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
(modification, inhibits)
Kurth et al., J Immunol 2000, Tanuma et al., J Biol Chem 2000, Pflanz et al., J Immunol 2000, Chow et al., Science 2001, Haan et al., J Biol Chem 2001, Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Schroers et al., Protein Sci 2005, Giese et al., J Cell Sci 2005, Murakami et al., Proc Natl Acad Sci U S A 1991, Tenhumberg et al., Biochem Biophys Res Commun 2006, Hibi et al., Cell 1990, Taga et al., Cell 1989, Guschin et al., EMBO J 1995, Horsten et al., FEBS Lett 1995, Ward et al., J Biol Chem 1994, Lütticken et al., Science 1994, Yawata et al., EMBO J 1993, Murakami et al., Science 1993, Horsten et al., J Biol Chem 1997, Rodig et al., Cell 1998, Kurth et al., J Immunol 1999
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA complex (IL6-IL6R)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
(modification, collaborate)
Kurth et al., J Immunol 2000, Tanuma et al., J Biol Chem 2000, Pflanz et al., J Immunol 2000, Chow et al., Science 2001, Haan et al., J Biol Chem 2001, Boulanger et al., Science 2003, Novotny-Diermayr et al., J Biol Chem 2005, Schroers et al., Protein Sci 2005, Giese et al., J Cell Sci 2005, Murakami et al., Proc Natl Acad Sci U S A 1991, Tenhumberg et al., Biochem Biophys Res Commun 2006, Hibi et al., Cell 1990, Taga et al., Cell 1989, Guschin et al., EMBO J 1995, Horsten et al., FEBS Lett 1995, Ward et al., J Biol Chem 1994, Lütticken et al., Science 1994, Yawata et al., EMBO J 1993, Murakami et al., Science 1993, Horsten et al., J Biol Chem 1997, Rodig et al., Cell 1998, Kurth et al., J Immunol 1999
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
Hck (HCK)
(modification, collaborate)
Schaeffer et al., Mol Cell Biol 2001
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/Hck complex (IL6-IL6R-IL6ST-JAK1-LMO4-HCK)
(modification, collaborate)
Schaeffer et al., Mol Cell Biol 2001
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
Hck (HCK)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/Hck complex (IL6-IL6R-IL6ST-JAK1-LMO4-HCK)
(modification, collaborate)
Schaeffer et al., Mol Cell Biol 2001
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
STAT3 (STAT3)
(modification, activates)
Jain et al., J Biol Chem 1999, Schuringa et al., J Biol Chem 2001, Novotny-Diermayr et al., J Biol Chem 2002, Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Yasukawa et al., Nat Immunol 2003, Novotny-Diermayr et al., J Biol Chem 2005, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1993, Zhong et al., Science 1994, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Kaptein et al., J Biol Chem 1996, Gerhartz et al., J Biol Chem 1996, Haan et al., J Biol Chem 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
nPKC-delta (PRKCD)
(modification, activates)
Jain et al., J Biol Chem 1999, Schuringa et al., J Biol Chem 2001, Novotny-Diermayr et al., J Biol Chem 2002, Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Yasukawa et al., Nat Immunol 2003, Novotny-Diermayr et al., J Biol Chem 2005, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1993, Zhong et al., Science 1994, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Kaptein et al., J Biol Chem 1996, Gerhartz et al., J Biol Chem 1996, Haan et al., J Biol Chem 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4 complex (IL6-IL6R-IL6ST-JAK1-LMO4)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, activates)
Jain et al., J Biol Chem 1999, Schuringa et al., J Biol Chem 2001, Novotny-Diermayr et al., J Biol Chem 2002, Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Yasukawa et al., Nat Immunol 2003, Novotny-Diermayr et al., J Biol Chem 2005, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1993, Zhong et al., Science 1994, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Kaptein et al., J Biol Chem 1996, Gerhartz et al., J Biol Chem 1996, Haan et al., J Biol Chem 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL6-mediated signaling events:
nPKC-delta (PRKCD)
→
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3 complex (IL6-IL6R-IL6ST-JAK1-LMO4-SOCS3)
(modification, activates)
Jain et al., J Biol Chem 1999, Schuringa et al., J Biol Chem 2001, Novotny-Diermayr et al., J Biol Chem 2002, Croker et al., Nat Immunol 2003, Lang et al., Nat Immunol 2003, Yasukawa et al., Nat Immunol 2003, Novotny-Diermayr et al., J Biol Chem 2005, Guschin et al., EMBO J 1995, Wegenka et al., Mol Cell Biol 1993, Zhong et al., Science 1994, Wegenka et al., Mol Cell Biol 1994, Lütticken et al., Science 1994, Kaptein et al., J Biol Chem 1996, Gerhartz et al., J Biol Chem 1996, Haan et al., J Biol Chem 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
Reactome Reaction:
IL6
→
IL6R
(direct_complex)
Taga et al., Cell 1989
-
Reactome Reaction:
IL6R
→
IL6
(reaction)
Taga et al., Cell 1989, Hemmann et al., J Biol Chem 1996, Schaper et al., Biochem J 1998
-
Reactome Reaction:
IL6R
→
IL6
(direct_complex)
Taga et al., Cell 1989
-
Reactome Reaction:
IL6
→
IL6R
(reaction)
Taga et al., Cell 1989, Hemmann et al., J Biol Chem 1996, Schaper et al., Biochem J 1998
-
WikiPathways Hepatitis C and Hepatocellular Carcinoma:
IL6
→
IL6R
(activation)
-
WikiPathways Senescence and Autophagy in Cancer:
IL6
→
IL6R
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Bind Interaction:
Complex of IL6ST-IL6R-IL6ST-IL6R-IL6-IL6
Skiniotis et al., Nature structural & molecular biology 2005*
-
IRef Bind Interaction:
IL6
—
IL6R
Skiniotis et al., Nature structural & molecular biology 2005*
-
IRef Bind Interaction:
IL6
—
IL6R
Boulanger et al., Science 2003
-
IRef Bind_translation Interaction:
IL6
—
IL6R
(molecular sieving)
Skiniotis et al., Nature structural & molecular biology 2005*
-
IRef Bind_translation Interaction:
IL6
—
IL6R
(x-ray crystallography)
Boulanger et al., Science 2003
-
IRef Biogrid Interaction:
IL6
—
IL6R
(direct interaction, pull down)
Schwantner et al., J Biol Chem 2004*
-
IRef Biogrid Interaction:
IL6
—
IL6R
(direct interaction, pull down)
Schuster et al., J Biol Chem 2003*
-
IRef Biogrid Interaction:
IL6
—
IL6R
(physical association, affinity chromatography technology)
Taga et al., Cell 1989
-
IRef Dip Interaction:
IL6
—
IL6R
(physical association, affinity chromatography technology)
Kalai et al., Blood 1997*
-
IRef Dip Interaction:
IL6
—
IL6R
(physical association, coimmunoprecipitation)
Ozbek et al., J Biol Chem 1998*
-
IRef Dip Interaction:
IL6
—
IL6R
(physical association, molecular sieving)
Ward et al., J Biol Chem 1996*
-
IRef Dip Interaction:
IL6
—
IL6R
(physical association, biochemical)
Paonessa et al., EMBO J 1995*
-
IRef Hprd Interaction:
Complex of IL6R-IL6ST-IL6R-IL6-IL6ST-IL6-IL6ST-IL6R-IL6
(in vivo)
Li et al., J Virol 2001*, Boulanger et al., Science 2003
-
IRef Hprd Interaction:
IL6
—
IL6R
(in vivo)
Boulanger et al., Science 2003, Schwantner et al., J Biol Chem 2004*
-
IRef Hprd Interaction:
IL6
—
IL6R
(in vitro)
Boulanger et al., Science 2003, Schwantner et al., J Biol Chem 2004*
-
IRef Innatedb Interaction:
IL6
—
IL6R
(unknown, -)
Salvati et al., J Biol Chem 1995*
-
IRef Innatedb Interaction:
IL6
—
IL6R
(unknown, -)
Kalai et al., Eur J Biochem 1996*
-
IRef Innatedb Interaction:
IL6
—
IL6R
(unknown, -)
Skiniotis et al., Nature structural & molecular biology 2005*
-
IRef Innatedb Interaction:
IL6
—
IL6R
(unknown, -)
Schwantner et al., J Biol Chem 2004*
-
IRef Innatedb Interaction:
IL6
—
IL6R
(unknown, -)
Ozbek et al., J Biol Chem 1998*
-
IRef Intact Interaction:
Complex of 13 proteins
(physical association, x-ray crystallography)
Boulanger et al., Science 2003
-
IRef Ophid Interaction:
IL6
—
IL6R
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
IL6
—
IL6R
(aggregation, confirmational text mining)
Li et al., J Virol 2001*
Text-mined interactions from Literome
Naruishi et al., J Periodontal Res 1999
(Chronic Disease...) :
Role of soluble
interleukin-6 receptor in inflamed gingiva for binding of
interleukin-6 to gingival fibroblasts
Ling et al., Crit Care Med 2002
:
In endotoxin treated rats, there was significant inhibition of
interleukin-6 activation of janus kinase-1, gp 130, the
interleukin-6 receptor , STAT1, and STAT3
Zohlnhöfer et al., FEBS Lett 1992
(Carcinoma, Hepatocellular) :
We studied the
role of
gp80 in binding, internalization and down-regulation of the hepatic
IL6-receptor (IL6R) by its ligand in human hepatoma cells ( HepG2 ) ... Comparison of transfected HepG2 cells overexpressing gp80 with parental cells indicate that
gp80 is
responsible for low affinity binding ( Kd = 500 pM ) of
IL6
Mackiewicz et al., FEBS Lett 1992
(Carcinoma, Hepatocellular...) :
Stable transfection of
IL-6-cDNA into HepG2 cells ( HepG2-IL-6 ) resulting in constitutive secretion of 2 micrograms of IL-6 per 10 ( 6 ) cells in 24 h
led to a down-regulation of surface bound
gp80 and subsequent homologous desensitization of HepG2-IL-6 cells towards IL-6
Kovacs et al., Biomed Pharmacother 2003
(Multiple Myeloma) :
How does
interleukin-6 affect the membrane expressions of
interleukin-6 receptor and gp130 and the proliferation of the human myeloma cell line OPM-2 ?
Zeng et al., Zhongguo Zhong Xi Yi Jie He Za Zhi 2005
(Osteoporosis) :
Beginning from the 2nd week, the osteoclasts formation in Group B was higher than that in Group A ( P < 0.05 ), and
IL-6 ,
IL-6R gene expression significantly
increased in Group B ( P < 0.05 or P < 0.01 )
Dovio et al., Eur J Endocrinol 2006
(Bone Resorption...) :
Soluble
IL-6Ralpha ( sIL-6Ralpha )
enhances , while sgp130 inhibits
IL-6 signalling
Kovacs et al., TheScientificWorldJournal 2006
(Lymphoma, B-Cell...) :
In this study, we investigated the
effects of IL-6, IL-6 receptor antagonist
(IL-6RA) , and gp130 antagonist (gp130A) on the membrane expressions of
IL-6R and gp130, on the viability, on the proliferation, on the DNA synthesis, and on the cell cycle phases in several multiple myeloma ( MM ) cell lines and B cell lymphoma cell lines
Ghazizadeh et al., J Invest Dermatol 2007
(Keloid) :
Induction of
IL-6 by IL-1beta peptide and stimulation by IL-6 peptide in NFs, or inhibition of IL-6 or
IL-6R alpha in KFs cultures demonstrated a dose dependent increase or decrease in procollagen I synthesis, respectively
Rabe et al., Blood 2008
(Acute Disease...) :
Here we developed a transgenic strategy based on the overexpression of the soluble form of gp130, which specifically blocks all
IL6 responses
mediated by the soluble
IL6R but does not affect IL6 responses via the membrane bound IL6R
Suh et al., J Cell Physiol 2009
:
IL-6 ( 10 ng/ml )
increased the level of
IL-6Ralpha and glycoprotein (gp) 130 ( IL-6Rbeta ) protein expressions
Dela Cruz et al., J Biol Chem 2009
:
Human
IL-6 , but not vIL-6,
requires IL-6Ralpha for binding to gp130
Buchholz et al., Neurogastroenterol Motil 2012
(Ileus...) :
However,
IL-6R blockade did not
prevent endotoxin associated mortality nor did it alter circulating
IL-6 levels
Stone et al., PloS one 2013
(Giant Lymph Node Hyperplasia) :
These elevated
interleukin-6 receptor levels may
contribute to increased
interleukin-6 activity through the trans signaling pathway
Egawa et al., Cytokine 1995
:
Our data suggest that the human IL-6R alpha-subunit
gp80 is
sufficient to confer high- and low-affinity
IL-6 binding to Xenopus laevis oocytes
Lasfar et al., Eur J Immunol 1994
(Multiple Myeloma) :
These data indicate that, in myeloma cells,
IL-6R are differentially
regulated by
IL-6 and IFN-alpha
Xi et al., Zhonghua Zhong Liu Za Zhi 1993
(Leukemia, Promyelocytic, Acute) :
The
effect of the recombinant
IL6-PE40 on both the LT12-IL6R+ cells and the IL6R- parental cells (
LT12-IL6R- ) was studied by leukemic progenitor colony ( CFU-L ) formation and 3H-TdR incorporation assays
Rose-John et al., J Biol Chem 1993
:
Retention of
IL-6 in the ER
led to the prevention of surface expression of the IL-6 receptor protein
gp80 , making these cells unresponsive to IL-6
Suzuki et al., Eur J Immunol 1993
(Autoimmune Diseases...) :
Serum soluble
interleukin-6 receptor in MRL/lpr mice is elevated with age and
mediates the
interleukin-6 signal
Cichy et al., Biochem Biophys Res Commun 1996
:
Effect of soluble
interleukin-6 receptor on
interleukin-6 synthesis in human skin fibroblasts ... In this study the ability of soluble
interleukin-6 receptor ( sIL-6R ) to
stimulate interleukin-6 (IL-6) synthesis in human fibroblasts is described
Gatsios et al., Eur J Biochem 1996
:
Interleukin-6 itself had no effect on synovial lining cells but a complex of
interleukin-6 and the soluble
interleukin-6 receptor induced
activation of signal transducer and activator of transcription ( STAT ) factors in these cells and regulated TIMP-1 and TIMP-3 expression in a similar fashion as oncostatin M
Sun et al., Eur Cytokine Netw 1997
:
All the
IL-6RA inhibited wild-type
IL-6
Feleder et al., Biol Signals Recept 1998
:
IL-6ra also
increased IL-6 levels measured in medium probably due to a decrease in the metabolization induced by the blockage of the receptors and the consequent accumulation of IL-6 in the media
Säily et al., Growth Factors 1998
(Leukemia, Myeloid, Acute) :
Expression of
interleukin-6 (IL-6) receptor gene in acute myeloblastic leukemia and
response of leukemic cells to exogenous
IL-6
Sawamura et al., J Immunol 1998
(Inflammation...) :
Furthermore, preintroduction of some mutant genes delayed the erythema induced by postintroduction of the wild-type IL-6 gene, suggesting that the mutant forms of
IL-6 prevent wild-type IL-6 from binding to
IL-6Ralpha
van der Meijden et al., Cell Immunol 1998
(HIV Infections) :
CD126 is
responsible for
IL-6 binding, and its expression determines which cells respond to this cytokine