p-5Y-RET-GRB2-containing complexes bind GAB1,GAB2

Stable Identifier
Reaction [omitted]
Homo sapiens
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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
Orthologous Events
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