Figure 7

Common and divergent biologic responses initiated by wild-type and mutant PDGFRα. Circos plot [68] representing the generated signalling/transcriptomic gene regulatory networks from the microarray analyses. The figure shows an overlay of the global PDGFRα-mutant regulatory network (common signature of the V561D and D842Y mutants) and the stimulated PDGFRα-wt regulatory network (see materials and methods section for details on network generation). Only SDEGs with a step-up FDR less than 0.05 and absolute fold change greater than 40% (in comparison to non-stimulated PDGFRα-wt control cells) are represented. The SDEGs were divided into three groups: 1) the common regulated genes between the oncogenic situation and the PDGF-AA stimulated wild-type protein (highlighted in light green), 2) SDEGs which are exclusively regulated under the oncogenic situation (red), 3) SDEGs which are only regulated for the PDGF-AA-stimulated (14 h) wild-type receptor (dark green). The average log2 transformed fold change between the corresponding situations and control is represented as a heat map in the two circles (outer heat map circle: merged V561D/D842Y; inner heat map circle: PDGF-AA stimulated receptor). The observed signalling characteristics are represented as conventional (violet) and unconventional (blue) signalling. The activation of these signalling components by the mutant or the wild-type receptors is indicated by green dots. The interactions between the molecules in the networks were visualized as violet (conventional signalling to transcriptomic responses), blue (unconventional signalling to transcriptomic responses) or grey (transcriptomic to transcriptomic) connections.