Reaction: CSF1R-associated SOS1 mediates exchange of GTP for GDP bound to RAS
- in pathway: Signaling by CSF1 (M-CSF) in myeloid cells
SOS1 (SOS) is stably bound to GRB2, which transiently associates with phosphorylated CSF1R. In response to the activation of CSF1R by CSF1, SOS1 promotes RAS to exchange of GDP for GTP (inferred from mouse homologs) and thereby activates the RAS-RAF-MEK-ERK1,2 signaling pathway. Myeloid cells contain the KRAS isoform of RAS. KRAS:GTP enhances proliferation of macrophages (inferred from mouse homologs).
GRB2 has been shown to bind phosphotyrosine-699 of CSF1R (phosphotyrosine-697 of mouse Csf1r), however phosphorylation of tyrosines 544, 559, and 807 of mouse Csf1r are together sufficient for the full proliferative response mediated via the RS-RAF-MEK-ERK1,2 pathway (Yu et al. 2012) and mouse Csf1r lacking phosophotyrosine-697 can still activate ERK (Lee and States 2000), Csf1r phosphotyrosine-697 (human CSF1R phosphotyrosine-699) is likely not the only GRB2:SOS binding site
GRB2 has been shown to bind phosphotyrosine-699 of CSF1R (phosphotyrosine-697 of mouse Csf1r), however phosphorylation of tyrosines 544, 559, and 807 of mouse Csf1r are together sufficient for the full proliferative response mediated via the RS-RAF-MEK-ERK1,2 pathway (Yu et al. 2012) and mouse Csf1r lacking phosophotyrosine-697 can still activate ERK (Lee and States 2000), Csf1r phosphotyrosine-697 (human CSF1R phosphotyrosine-699) is likely not the only GRB2:SOS binding site
Reaction - small molecule participants:
GDP [cytosol]
GTP [cytosol]
Reactome.org reaction link: R-HSA-9680385
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Reaction input - small molecules:
GTP(4-)
Reaction output - small molecules:
GDP(3-)
Reactome.org link: R-HSA-9680385