EPO:phospho-EPOR:phospho-JAK2:LYN:IRS2:phospho-CRKL:RAPGEF1:GRB2-1:SOS1,phospho-VAV1 mediates exchange of GTP for GDP bound to RAS

Stable Identifier
R-HSA-9029158
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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EPO:phospho-EPOR:phospho-JAK2:LYN:IRS2:phospho-CRKL:RAPGEF1:GRB2-1:SOS1,phospho-VAV1 mediates exchange of GTP for GDP bound to RAS
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SOS1 and phospho-VAV1 bound to GRB2 in a complex with the activated EPOR catalyze the exchange of GDP for GTP bound to RAS proteins, yielding RAS:GTP (Komatsu et al. 1992, Torti et al. 1992). RAS:GTP then activates RAF1 and ERK1 and ERK2. EPO is observed to activate HRAS (Komatsu et al. 1992, Torti et al. 1992), KRAS, and NRAS (inferred from mouse homologs). KRAS appears to be particularly important for erythropoiesis since deletion of KRAS causes anemia in mouse.
Literature References
PubMed ID Title Journal Year
1569084 Erythropoietin induces p21ras activation and p120GAP tyrosine phosphorylation in human erythroleukemia cells

Torti, M, Marti, KB, Altschuler, D, Yamamoto, K, Lapetina, EG

J. Biol. Chem. 1992
1377053 Erythropoietin rapidly induces tyrosine phosphorylation in the human erythropoietin-dependent cell line, UT-7

Komatsu, N, Adamson, JW, Yamamoto, K, Altschuler, D, Torti, M, Marzocchini, R, Lapetina, EG

Blood 1992
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Input
Output
Participates
as an event of
Catalyst Activity

guanyl-nucleotide exchange factor activity of EPO:p-8Y-EPOR:p-12Y-JAK2:LYN:IRS2:p-CRKL:RAPGEF1:p-Y-SHC1:GRB2:SOS1,p-Y-VAV1 [plasma membrane]

Physical Entity
EPO:p-8Y-EPOR:p-12Y-JAK2:LYN:IRS2:p-CRKL:RAPGEF1:p-Y-SHC1:GRB2:SOS1,p-Y-VAV1 [plasma membrane] (Homo sapiens)
Activity
guanyl-nucleotide exchange factor activity (GO:0005085)
Inferred From
Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2:p-Y-Crkl:p-Y-Shc1:Grb2-1:Sos1,p-Y-Vav1 mediates exchange of GDP for GTP bound to Ras (Mus musculus)
Authored
May, B  (2017-11-11)
Reviewed
McGraw, KL  (2018-08-14)
Created
May, B  (2017-11-14)
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