Erythropoietin activates RAS

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

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

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

Blood 1997
25887776 Emerging EPO and EPO receptor regulators and signal transducers

Wojchowski, DM, Kuhrt, D

Blood 2015
8677749 Proto-oncogene products Vav and c-Cbl are involved in the signal transduction through Grb2/Ash in hematopoietic cells

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

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

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

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

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

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

J. Biol. Chem. 1994
Event Information
Orthologous Events
Cross References
BioModels Database
Cite Us!