Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth

@article{citeulike:2802779, abstract = {Cannabinoid receptor 1 (CB1R) regulates neuronal differentiation. To understand the logic underlying decision-making in the signaling network controlling CB1R-induced neurite outgrowth, we profiled the activation of several hundred transcription factors after cell stimulation. We assembled an in silico signaling network by connecting CB1R to 23 activated transcription factors. Statistical analyses of this network predicted a role for the breast cancer 1 protein BRCA1 in neuronal differentiation and a new pathway from CB1R through phosphoinositol 3-kinase to the transcription factor paired box 6 (PAX6). Both predictions were experimentally confirmed. Results of transcription factor activation experiments that used pharmacological inhibitors of kinases revealed a network organization of partial OR gates regulating kinases stacked above AND gates that control transcription factors, which together allow for distributed decision-making in CB1R-induced neurite outgrowth. 10.1126/science.1152662}, author = {Bromberg, Kenneth D. and Ma'ayan, Avi and Neves, Susana R. and Iyengar, Ravi }, citeulike-article-id = {2802779}, doi = {10.1126/science.1152662}, journal = {Science}, keywords = {cisreg, network}, month = {May}, number = {5878}, pages = {903--909}, posted-at = {2008-05-15 23:42:10}, priority = {2}, title = {Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth}, url = {http://dx.doi.org/10.1126/science.1152662}, volume = {320}, year = {2008} }

TY - JOUR ID - citeulike:2802779 L3 - citeulike-article-id:2802779 TI - Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth JF - Science VL - 320 IS - 5878 SP - 903 EP - 909 N2 - Cannabinoid receptor 1 (CB1R) regulates neuronal differentiation. To understand the logic underlying decision-making in the signaling network controlling CB1R-induced neurite outgrowth, we profiled the activation of several hundred transcription factors after cell stimulation. We assembled an in silico signaling network by connecting CB1R to 23 activated transcription factors. Statistical analyses of this network predicted a role for the breast cancer 1 protein BRCA1 in neuronal differentiation and a new pathway from CB1R through phosphoinositol 3-kinase to the transcription factor paired box 6 (PAX6). Both predictions were experimentally confirmed. Results of transcription factor activation experiments that used pharmacological inhibitors of kinases revealed a network organization of partial OR gates regulating kinases stacked above AND gates that control transcription factors, which together allow for distributed decision-making in CB1R-induced neurite outgrowth. 10.1126/science.1152662 KW - cisreg KW - network AU - Bromberg, Kenneth AU - Ma'ayan, Avi AU - Neves, Susana AU - Iyengar, Ravi PY - 2008/05/16/ UR - http://dx.doi.org/10.1126/science.1152662 ER -