Meta-Biol

• Pathways

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).