signal processing in the tgf-β superfamily ligand-receptor network信号处理在tgf-β总科中的网络.pdfVIP

Signal Processing in the TGF-b Superfamily Ligand-Receptor Network 1* 2 2 Jose M. G. Vilar , Ronald Jansen , Chris Sander 1 Integrative Biological Modeling Laboratory, Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 2 Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America The TGF-b pathway plays a central role in tissue homeostasis and morphogenesis. It transduces a variety of extracellular signals into intracellular transcriptional responses that control a plethora of cellular processes, including cell growth, apoptosis, and differentiation. We use computational modeling to show that coupling of signaling with receptor trafficking results in a highly versatile signal-processing unit, able to sense by itself absolute levels of ligand, temporal changes in ligand concentration, and ratios of multiple ligands. This coupling controls whether the response of the receptor module is transient or permanent and whether or not different signaling channels behave independently of each other. Our computational approach unifies seemingly disparate experimental observations and suggests specific changes in receptor trafficking patterns that can lead to phenotypes that favor tumor progression. Citation: Vilar JMG, Jansen R, Sander C (2006) Signal processing in the TGF-b superfamily ligand-receptor network. PLoS Comput Biol 2(1): e3. Introduction function from suppressor to promoter of growth in epithelial cells during tumor progression [4,5]. The TGF-b signal transduction pathway follows an appa- Cu