Epo binds Epor:Jak2:Lyn:Irs2

Stable Identifier
R-MMU-9006326
Type
Reaction [binding]
Species
Mus musculus
Compartment
plasma membrane
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Epo binds Epor:Jak2:Lyn:Irs2
Extracellular Erythropoietin (Epo) binds the Epo receptor (Epor) located in the plasma membrane of the target cell (D'Andrea et al. 1989). Epor is a dimer (Livnah et al. 1999, Constantinescu et al. 2001) that appears to be preassociated with downstream signaling proteins Jak2 (Witthuhn et al. 1993, Miura et al. 1994, Sawyer and Penta 1996, Pelletier et al. 2006) and Lyn (Tilbrook et al. 1997, Chin et al. 1998, Tilbrook et al. 2001) and the scaffold protein Irs2 (Verdier et al. 1997). Binding of Epo to Epor causes a change in the conformation of the dimer which activates Jak2 (Witthuhn et al. 1993, Seubert et al. 2003, Kubatzky et al. 2005, Lu et al. 2005, Lu et al. 2006).
Literature References
PubMed ID Title Journal Year
11296286 Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain

Constantinescu, SN, Keren, T, Socolovsky, M, Nam, H, Henis, YI, Lodish, HF

Proc. Natl. Acad. Sci. U.S.A. 2001
16982687 Two domains of the erythropoietin receptor are sufficient for Jak2 binding/activation and function

Pelletier, S, Gingras, S, Funakoshi-Tago, M, Howell, S, Ihle, JN

Mol. Cell. Biol. 2006
15657048 Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function

Kubatzky, KF, Liu, W, Goldgraben, K, Simmerling, C, Smith, SO, Constantinescu, SN

J. Biol. Chem. 2005
8943308 Association of JAK2 and STAT5 with erythropoietin receptors. Role of receptor phosphorylation in erythropoietin signal transduction

Sawyer, ST, Penta, K

J. Biol. Chem. 1996
8343951 JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin

Witthuhn, BA, Quelle, FW, Silvennoinen, O, Yi, T, Tang, B, Miura, O, Ihle, JN

Cell 1993
2539263 Expression cloning of the murine erythropoietin receptor

D'Andrea, AD, Lodish, HF, Wong, GG

Cell 1989
9130706 Lyn tyrosine kinase is essential for erythropoietin-induced differentiation of J2E erythroid cells

Tilbrook, PA, Ingley, E, Williams, JH, Hibbs, ML, Klinken, SP

EMBO J. 1997
16414957 Active conformation of the erythropoietin receptor: random and cysteine-scanning mutagenesis of the extracellular juxtamembrane and transmembrane domains

Lu, X, Gross, AW, Lodish, HF

J. Biol. Chem. 2006
9334184 Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation

Verdier, F, Chrétien, S, Billat, C, Gisselbrecht, S, Lacombe, C, Mayeux, P

J. Biol. Chem. 1997
11289114 Maturation of erythroid cells and erythroleukemia development are affected by the kinase activity of Lyn

Tilbrook, PA, Palmer, GA, Bittorf, T, McCarthy, DJ, Wright, MJ, Sarna, MK, Linnekin, D, Cull, VS, Williams, JH, Ingley, E, Schneider-Mergener, J, Krystal, G, Klinken, SP

Cancer Res. 2001
9974392 Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation

Livnah, O, Stura, EA, Middleton, SA, Johnson, DL, Jolliffe, LK, Wilson, IA

Science 1999
9573010 Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway

Chin, H, Arai, A, Wakao, H, Kamiyama, R, Miyasaka, N, Miura, O

Blood 1998
14636581 Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer

Seubert, N, Royer, Y, Staerk, J, Kubatzky, KF, Moucadel, V, Krishnakumar, S, Smith, SO, Constantinescu, SN

Mol. Cell 2003
Participants
Input
Output
Orthologous Events
EPO binds EPOR:JAK2:LYN:IRS2 (Homo sapiens)
Authored
May, B  (2017-04-22)
Reviewed
McGraw, KL  (2018-08-14)
Created
May, B  (2017-05-13)
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