SPRY2 binds GRB2

Stable Identifier
R-HSA-1295613
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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SPRY2 binds GRB2
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Some evidence suggests that SPRY2 may exert its negative effect by binding to GRB2 and competing with the GRB2:SOS1 interaction that is required for MAPK activation. SPRY2 phosphorylation at Y55 is stimulated in response to both FGF and EGF, and is required for SPRY2 to act as a negative regulator of FGF signaling. Y55 is not thought to be a GRB2 binding site, however. Instead, phosphorylation at Y55 is thought to cause a conformational change in SPRY2 that reveals a cryptic PXXPXPR GRB2-docking site in the C-terminal of SPRY2.
SPRY2 has also been shown to be phosphorylated at multiple tyrosine residues in its C-terminal in response to FGF, but not EGF, stimulation. This phosphorylation, in particular at residue 227, is thought to augment the ability of SPRY2 to inhibit FGF signaling through the MAPK cascade, although the mechanism remains to be elucidated.
Literature References
PubMed ID Title Journal Year
15637081 Phosphorylation of carboxyl-terminal tyrosines modulates the specificity of Sprouty-2 inhibition of different signaling pathways

Yarden, Y, Ron, D, Vaisman, N, Zwang, Y, Rubin, C

J Biol Chem 2005
16893902 A Src homology 3-binding sequence on the C terminus of Sprouty2 is necessary for inhibition of the Ras/ERK pathway downstream of fibroblast growth factor receptor stimulation

Saw, TY, Yusoff, P, Lao, DH, Fong, CW, Chandramouli, S, Yu, CY, Leong, HF, Tai, LP, Guy, GR

J Biol Chem 2006
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Orthologous Events
SPRY2 binds GRB2 (Bos taurus)
SPRY2 binds GRB2 (Canis familiaris)
SPRY2 binds GRB2 (Danio rerio)
SPRY2 binds GRB2 (Drosophila melanogaster)
SPRY2 binds GRB2 (Mus musculus)
SPRY2 binds GRB2 (Rattus norvegicus)
SPRY2 binds GRB2 (Sus scrofa)
SPRY2 binds GRB2 (Xenopus tropicalis)
Authored
Rothfels, K  (2011-08-15)
Reviewed
Gotoh, N  (2011-08-26)
Created
Rothfels, K  (2011-05-18)
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