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Figure 1

Figure 1. From: Navigating the network: signaling cross-talk in hematopoietic cells.

Topology of signaling networks and interpretation of experimental readouts. (a) Representation of signaling pathway schema from simple linear pathways (Rx), to branched pathways downstream of multicomponent receptor complexes (Ry), to signaling networks (Rz). Multiple pathways can either induce distinct transcriptional signatures or converge on common genes. Feedback from induced transcripts can occur at the level of autocrine and/or paracrine actions of secreted proteins or at the level of direct effects on cytoplasmic signaling components. Several aspects of network architecture include the importance of scaffold proteins for interpathway insulation and how multiple pathways may ‘share’ common signaling components. (b) Continuous gene-versus-phenotype relationship from genome-wide RNAi screen for signaling regulators in Drosophila melanogaster cells (reproduced from ref. 41). The effect of dsRNA targeting 24,000 genes is represented as a Z-score relative to control Erk activation. Canonical pathway signaling components and regulators are identified at the extremes of the distribution. The physiological influence of genes in the central section is discussed in the text. (c) Effects of various degrees of stimulus on a hypothetical signaling pathway ‘canonical’ target and an ‘off-pathway’ target. Whereas the off-pathway target can induce a measurable response under high-dose conditions, only the canonical target induces a response in the physiological dose range.

Iain D C Fraser, et al. Nat Immunol. ;10(4):327-331.

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