Erythropoietin activates RAS

Stable Identifier
R-HSA-9027284
Type
Pathway
Species
Homo sapiens
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The RAS guanine nucleotide exchange factors SOS1 and VAV1 bind indirectly to the phosphorylated EPOR via CRKL, SHC1, and GRB2 (Miura et al. 1994, Hanazono et al. 1996, Odai et al. 1997, Arai et al. 2001, reviewed in Kuhrt et al. 2015) . The phosphorylated cytoplasmic domain of EPOR binds CRKL, which is then phosphorylated (Arai et al. 2001). Phosphorylated CRKL binds SHC1, which is then phosphorylated and binds either GRB2:SOS1 (Barber et al. 1997) or GRB2:VAV1 (Hanazono et al. 1996). SOS1 and phosphorylated VAV1 catalyze the exchange of GDP for GTP bound to RAS, that is, RAS:GDP is converted to RAS:GTP.

Literature References
PubMed ID Title Journal Year
25887776 Emerging EPO and EPO receptor regulators and signal transducers

Kuhrt, D, Wojchowski, DM

Blood 2015
8978277 Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells

Barber, DL, Corless, CN, Xia, K, Roberts, TM, D'Andrea, AD

Blood 1997
8677749 Proto-oncogene products Vav and c-Cbl are involved in the signal transduction through Grb2/Ash in hematopoietic cells

Hanazono, Y, Odai, H, Sasaki, K, Iwamatsu, A, Yazaki, Y, Hirai, H

Acta Haematol. 1996
11443118 CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling

Arai, A, Kanda, E, Nosaka, Y, Miyasaka, N, Miura, O

J. Biol. Chem. 2001
9209406 The signal transduction through Grb2/Ash in hematopoietic cells

Odai, H, Hanazono, Y, Sasaki, K, Iwamatu, A, Yazaki, Y, Hirai, H

Leukemia 1997
7961995 Activation of the mitogen-activated protein kinase pathway by the erythropoietin receptor

Miura, Y, Miura, O, Ihle, JN, Aoki, N

J. Biol. Chem. 1994
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Orthologous Events
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