Signal processing in the TGF-beta superfamily ligand-receptor network.
The TGF-beta 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.
Vilar
Jose M G
JM
Integrative Biological Modeling Laboratory, Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. vilar@cbio.mskcc.org
Jansen
Ronald
R
Sander
Chris
C
D003198:Computer Simulation; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000145:classification* / Q000378:metabolism*
D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta