g-protein coupled receptor signaling architecture of mammalian immune cellsg蛋白耦合的哺乳动物免疫细胞受体信号的架构.pdfVIP

G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells 1,2 3 1 1,2 Natalia Polouliakh , Richard Nock , Frank Nielsen , Hiroaki Kitano * 1 Sony Computer Science Laboratories Inc., Tokyo, Japan, 2 Systems Biology Institute, Tokyo, Japan, 3 CEREGMIA- Univ. Antilles-Guyane, Schoelcher, France Abstract A series of recent studies on large-scale networks of signaling and metabolic systems revealed that a certain network structure often called ‘‘bow-tie network’’ are observed. In signaling systems, bow-tie network takes a form with diverse and redundant inputs and outputs connected via a small numbers of core molecules. While arguments have been made that such network architecture enhances robustness and evolvability of biological systems, its functional role at a cellular level remains obscure. A hypothesis was proposed that such a network function as a stimuli-reaction classifier where dynamics of core molecules dictate downstream transcriptional activities, hence physiological responses against stimuli. In this study, we examined whether such hypothesis can be verified using experimental data from Alliance for Cellular Signaling (AfCS) that comprehensively measured GPCR related ligands response for B-cell and macrophage. In a GPCR signaling system, cAMP and Ca2+ act as core molecules. Stimuli-response for 32 ligands to B-Cells and 23 ligands to macrophages has been measured. We found that ligands with correlated changes of cAMP and Ca2+ tend to cluster closely together within the hyperspaces of both cell types and they induced genes involved in the same cellular processes. It was found that ligands inducing cAMP synthesis activate genes involved in cell growth and proliferation; cAMP and C