PRMT5 is tyrosine phosphorylated by JAK2 V617F

Stable Identifier
R-HSA-3215391
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Tyrosine phosphorylation of PRMT5 can block WDR77 (MEP50) binding, which attenuates PRMT5 activity (Liu et al. 2011). The kinase JAK2 is constitutively activated by the mutation V617F, observed in most patients with non-chronic myelogenous leukemia (nCML) myeloproliferative neoplasms (MPNs) (Liu et al. 2011). JAK2 V617F can phosphorylate STAT5 in the absence of upstream signals, which confers cytokine-independent growth to Ba/F3 cells and induces a myeloproliferative disease in mouse models (Akada et al. 2010, Marty et al., 2010, Mullally et al. 2010). JAK2 V617F phosphorylates PRMT5 predominantly at tyrosines 297, 304, and 307, significantly reducing the activity-enhancing interaction between PRMT5 and WDR77 (MEP50) (Liu et al. 2011).

Literature References
PubMed ID Title Journal Year
21316606 JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation

Liu, F, Zhao, X, Perna, F, Wang, L, Koppikar, P, Abdel-Wahab, O, Harr, MW, Levine, RL, Xu, H, Tefferi, A, Deblasio, A, Hatlen, M, Menendez, S, Nimer, SD

Cancer Cell 2011
Participants
Participates
Catalyst Activity

protein tyrosine kinase activity of JAK2 V617F [nucleoplasm]

Functional status

Gain of function of JAK2 V617F [nucleoplasm]

Disease Entity