  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.
