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The AfCS completed an analysis of context dependent signaling in RAW cells (see our recent paper). The Macrophage-like cells were exposed to 22 different ligands singly or in pairs. And the kinetics of specific protein phosphorylation, second messenger accumulation, global and specific changes in transcription and cytokine release were all measured and the responses to single and multiple ligand addition were compared. These experiments were designed to reveal the architecture of the signaling circuitry that regulates cellular responses to physiologically relevant ligands. The goal of the AfCS is to understanding the mechanisms that underlie context dependent signaling, and thus underlie the cells complex responses to physiological and pharmacological agents. The resources of the AFCS going forward are limited and thus we have concentrated on defining and developing mechanistic models for the interactions involved in the operation of the subnet of G protein mediated signaling. We are focusing on a few of the "outputs" or end products of G-protein mediated signaling - intracellular cAMP, Calcium, and modulation of Cytokine release.

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