PRMT5 is tyrosine phosphorylated by JAK2 V617F

Stable Identifier
R-HSA-3215391
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
PRMT5 is tyrosine phosphorylated by JAK2 V617F
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
protein tyrosine kinase activity of JAK2 V617F [nucleoplasm]
Physical Entity
JAK2 V617F [nucleoplasm]
Activity
protein tyrosine kinase activity (0004713)
Disease
Name Identifier Synonyms
chronic myeloid leukemia 8552 CML, chronic myelogenous leukemia, no ICD-O subtype (morphologic abnormality), chronic myeloid leukemia, disease (disorder), chronic myeloid leukemia without mention of remission, CML - chronic Myelogenous Leukemia, chronic myeloid leukemia in remission (disorder), Myeloid Leukemia, chronic, CML in Remission, chronic myeloid leukemia in remission, chronic myeloid leukaemia, chronic myeloid leukemia NOS (disorder)
Authored
Jupe, S  (2013-03-12)
Reviewed
Guccione, E  (2014-05-09)
Fischle, W  (2014-07-23)
Created
Jupe, S  (2013-03-15)