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SOCS3 binds IL6ST
Stable Identifier
R-HSA-1112755
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane
,
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
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Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-6 family signaling (Homo sapiens)
Interleukin-6 signaling (Homo sapiens)
SOCS3 binds IL6ST (Homo sapiens)
General
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Suppressor of cytokine signaling protein 3 (SOCS3) binds to the same IL6ST (gp130) phosphotyrosine (Tyr-759) as PTPN11 (SHP2) (Schmitz et al. 2000) though they appear to suppress Interleukin-6 (IL6) signaling by independent mechanisms (Lehmann et al. 2003). Members of the SOCS family (CIS and SOCS1-7) have an N-terminal SH2 domain preceded by an extended SH2 domain (ESS) and kinase inhibitory region (KIR) (Hilton et al. 1998). The related SOCS1 associates with JAKs via its KIR and SH2 domains (Narazaki et al. 1998, Yasukawa et al. 1999) leading to inhibition of JAK signaling and kinase activity. SOCS3 was unable to inhibit JAK kinase activity in vitro, suggesting that SOCS1 and SOCS3 inhibit signaling in different ways (Nicholson et al. 1999), but it is possible that SOCS3's inhibitory actions require binding to both activated receptor gp130 Tyr-759 and the associated JAK for maximal inhibition (Greenhalgh & Hilton 2001). Socs3 deficiency results in prolonged STAT1/3 activation after IL6 but not interferon-gamma (IFNG) stimulation suggesting that SOCS3 has a role in preventing IFNG-like responses in cells stimulated by IL6 (Croker et al. 2003).
Literature References
PubMed ID
Title
Journal
Year
10777583
SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130
Schaper, F
,
Heinrich, PC
,
Haan, S
,
Weissenbach, M
,
Schmitz, J
J Biol Chem
2000
Participants
Input
SOCS3 [cytosol]
(Homo sapiens)
Tyrosine phosphorylated IL6 receptor hexamer:Activated JAKs [plasma membrane]
(Homo sapiens)
Output
Tyrosine phosphorylated IL6 receptor hexamer:Activated JAKs:SOCS3 [plasma membrane]
(Homo sapiens)
Participates
as an event of
Interleukin-6 signaling (Homo sapiens)
Orthologous Events
SOCS3 binds IL6ST (Bos taurus)
SOCS3 binds IL6ST (Canis familiaris)
SOCS3 binds IL6ST (Danio rerio)
SOCS3 binds IL6ST (Gallus gallus)
SOCS3 binds IL6ST (Mus musculus)
SOCS3 binds IL6ST (Rattus norvegicus)
SOCS3 binds IL6ST (Sus scrofa)
SOCS3 binds IL6ST (Xenopus tropicalis)
Authored
Ray, KP (2010-12-13)
Reviewed
Rose-John, S (2011-02-11)
Created
Jupe, S (2010-12-10)
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