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SHC1 in the RET complex is phosphorylated
Stable Identifier
R-HSA-8854981
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
,
extracellular region
,
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
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Developmental Biology (Homo sapiens)
Nervous system development (Homo sapiens)
Axon guidance (Homo sapiens)
RET signaling (Homo sapiens)
SHC1 in the RET complex is phosphorylated (Homo sapiens)
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GDNF stimulation of neuronal cells induces the assembly of a large protein complex containing RET, GRB2 and tyrosine-phosphorylated SHC1, p85 subunit of (PI3K), GAB2 (GAB1 in Hayashi et al. 2000), and Tyrosine-protein phosphatase non-receptor type 11 (PTPN11, SHP-2) (Besset et al. 2000). Based on the mechanism of SHC1 activation in other receptor systems (Gu et al. 2000) it is likely that SHC1 tyrosine (Y) phosphorylation occurs as a consequence of RET binding and is required for subsequent events. GRB2 binding to SHC1 requires phosphorylation of Y349, Y350 and/or Y427 (Gu et al. 2000). Mutation of RET Y1062, which binds SHC1 to initiate recruitment of GRB2-GAB-p85, did not completely abolish the activation of RAS-RAF-ERK and PI3K-AKT (Besset et al. 2000), suggesting there are alternative pathways that do not utilize SHC1. RET has been shown to bind GRB2 directly, via Y1096 (Alberti et al. 1998, Besset et al. 2000).
It has not been established whether SHC1 associates with RET in phosphorylated form or is phosphorylated after binding, and the identity of the kinase is unknown, hence this is represented as an uncertain event.
Literature References
PubMed ID
Title
Journal
Year
10995764
Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase
Scott, RP
,
Ibáñez, CF
,
Besset, V
J. Biol. Chem.
2000
Participants
Input
2x p-5Y-RET:GDNF:GFRA complexes:SHC1 [plasma membrane]
(Homo sapiens)
Output
2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 [plasma membrane]
(Homo sapiens)
Participates
as an event of
RET signaling (Homo sapiens)
Orthologous Events
SHC1 in the RET complex is phosphorylated (Bos taurus)
SHC1 in the RET complex is phosphorylated (Canis familiaris)
SHC1 in the RET complex is phosphorylated (Drosophila melanogaster)
SHC1 in the RET complex is phosphorylated (Gallus gallus)
SHC1 in the RET complex is phosphorylated (Mus musculus)
SHC1 in the RET complex is phosphorylated (Rattus norvegicus)
SHC1 in the RET complex is phosphorylated (Sus scrofa)
SHC1 in the RET complex is phosphorylated (Xenopus tropicalis)
Authored
Jupe, S (2016-01-25)
Reviewed
Luo, W (2016-05-17)
Morales, D (2016-05-06)
Created
Jupe, S (2016-01-29)
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