Skip to main content
. 2016 May 27;473(11):1579–1591. doi: 10.1042/BCJ20160085

Figure 6. V617F-induced activation circuit.

Figure 6

(A) Schematic representation the V617F activation circuit. (B) Model of the interface between JH1 (blue) and JH2 (green) from MD simulation data (11). E596 (pink) interacts with the C-terminus of the SH2-JH2 linker (grey) and initiates a cascade of activating events involving residues F537 (purple), E543, D569, Y570, K883, K857 (red). (C) Y2A cells were transiently transfected with the JAK2 variants and STAT5 transcriptional reporter. E596R mutation decreases the activity of the different hyperactive JAK2 mutants that comprise the V617F activation circuit without impairing Epo normal response. (D) Y2A cells were transiently transfected with several JAK2 oncogenic mutants and basal transcriptional activity was measured with STAT5 transcriptional reporter, Spi_Luc. K539L, T875N and R683G all induce constitutive signalling of JAK2. No significant decrease in the constitutive activation of these mutants is observed when substituting E596 with either alanine or arginine. Shown in (C) and (D) are average units+S.E.M. for three independent experiments performed in triplicate (****P<0.0001, n.s, not significant; Dunn's multiple comparison test).