Jak2 transphosphorylates and is activated in response to Erythropoietin

Stable Identifier
R-MMU-9006329
Type
Reaction [transition]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
Jak2 transphosphorylates and is activated in response to Erythropoietin

Upon binding Epo, the Epor dimer changes conformation resulting in activation by phosphorylation of Jak2 associated with box 1 and box 2 of the cytoplasmic domain of each Epor (Yoshimura and Lodish 1992, Witthuhn et al. 1993, Miura et al. 1994, Sawyer and Penta 1996, Tilbrook et al. 1996, Bittorf et al. 1997, Watowich et al. 1999, Pelletier et al. 2006, Funakoshi-Tago et al. 2008, Zhao et al. 2009). One Jak2 transphosphorylates 12 tyrosine residues of the other Jak2 thereby activating Jak2 to phosphorylate Epor and other substrates (Feng et al. 1997).

Literature References
PubMed ID Title Journal Year
9067635 Requirement for JAK2 in erythropoietin-induced signalling pathways

Bittorf, T, Jaster, R, L├╝dtke, B, Kamper, B, Brock, J

Cell. Signal. 1997
1310150 In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130

Yoshimura, A, Lodish, HF

Mol. Cell. Biol. 1992
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
9111318 Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop

Feng, J, Witthuhn, BA, Matsuda, T, Kohlhuber, F, Kerr, IM, Ihle, JN

Mol Cell Biol 1997
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
19638629 A JAK2 interdomain linker relays Epo receptor engagement signals to kinase activation

Zhao, L, Dong, H, Zhang, CC, Kinch, L, Osawa, M, Iacovino, M, Grishin, NV, Kyba, M, Huang, LJ

J. Biol. Chem. 2009
8068943 Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo

Miura, O, Nakamura, N, Quelle, FW, Witthuhn, BA, Ihle, JN, Aoki, N

Blood 1994
10026152 Oligomerization and scaffolding functions of the erythropoietin receptor cytoplasmic tail

Watowich, SS, Liu, KD, Xie, X, Lai, SY, Mikami, A, Longmore, GD, Goldsmith, MA

J. Biol. Chem. 1999
18160720 Jak2 FERM domain interaction with the erythropoietin receptor regulates Jak2 kinase activity

Funakoshi-Tago, M, Pelletier, S, Moritake, H, Parganas, E, Ihle, JN

Mol. Cell. Biol. 2008
9052992 Regulation of the erythropoietin receptor and involvement of JAK2 in differentiation of J2E erythroid cells

Tilbrook, PA, Bittorf, T, Callus, BA, Busfield, SJ, Ingley, E, Klinken, SP

Cell Growth Differ. 1996
Participants
Catalyst Activity

protein tyrosine kinase activity of Epo:Epor:Jak2:Lyn:Irs2 [plasma membrane]

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