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p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2
Stable Identifier
R-HSA-8854897
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)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Homo sapiens)
General
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Grb-associated binder (GAB) proteins are a family of docking proteins that transduce cellular signals between receptors and intracellular downstream effectors (Ding et al. 2015). When phosphorylated by protein-tyrosine kinases, GABs can recruit several Src homology-2 (SH2) domain-containing proteins, including Tyrosine-protein phosphatase non-receptor type 11 (PTPN11, SHP2), the p85 subunit of phosphoinositide-3 kinase (p85-PI3K), phospholipase C-gamma 1 (PLCG1), CRK and GAB-associated Cdc42/Rac GTPase-activating protein (ARHGAP32, GC-GAP). These interactions lead to various downstream signals involved in cell growth, differentiation, migration and apoptosis.
GDNF stimulation of neuronal cells induces the assembly of a large protein complex containing RET, GRB2 and tyrosine-phosphorylated SHC1, p85-PI3K, GAB2 (GAB1 in Hayashi et al. 2000) and PTPN11 (Besset et al. 2000). GAB1 was found in complexes with GRB2 only after GDNF treatment (Hayashi et al. 2000). This contrasts with reports that GAB2 constitutively associates with GRB2 (Gu et al. 1998).
The likely order of recruitment to RET is SHC1, GRB2, GAB1/2, p85-PI3K, similar to the signaling mechanism of the Interleukin-3 receptor (Gu et al. 2000) and many others (Adams et al. 2012, Ding et al. 2015). As the order of RET complex formation is not firmly established, GAB binding is shown 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 with, without p-SHC1:GRB2-1 [plasma membrane]
(Homo sapiens)
GAB1,GAB2 [cytosol]
(Homo sapiens)
Output
2x p-5Y-RET:GDNF:GFRA complexes with, without p-SHC1:GRB2-1:GAB1,GAB2 [plasma membrane]
(Homo sapiens)
Participates
as an event of
RET signaling (Homo sapiens)
Orthologous Events
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Bos taurus)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Canis familiaris)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Drosophila melanogaster)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Gallus gallus)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Mus musculus)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Rattus norvegicus)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (Sus scrofa)
p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2 (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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