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. 2020 Sep 18;9:F1000 Faculty Rev-1153. [Version 1] doi: 10.12688/f1000research.26648.1

Figure 4. JAK2 regulates dimerization of the EPOR–JAK2 complex.

Figure 4.

( A) Normal EPOR–JAK2 complexes are inert without EPO. ( B) EPO binding to EPOR stabilizes the EPOR–JAK2 complex and triggers downstream signaling by activating JAK2. Colored circles represent normalized activation levels of EPOR signaling targets. ( C) Myeloproliferative neoplasm (MPN)-associated mutations in the JAK2 pseudokinase domain, which does not interact directly with EPOR, stabilize dimerization of EPOR–JAK2 complexes and activate JAK2 in the absence of EPO. Mutations in the linker region separating the FERM-SH2 and pseudokinase domains (exon 12) act similarly (not shown). Constitutive activation of the EPOR by MPN-associated mutations causes abnormal downstream signaling relative to that induced by EPO 142– 146. EPO, erythropoietin; EPOR, erythropoietin receptor.