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Living cells sense their environment through the binding of extra-cellularmolecular ligands to cell surface receptors. Puzzlingly, vast numbers ofsignaling pathways exhibit a high degree of cross talk between differentsignals whereby different ligands act through the same receptor or sharedcomponents downstream. It remains unclear how a cell can accurately processinformation from the environment in such cross-wired pathways. We show that afeature which commonly accompanies cross talk - signaling pleiotropy (theability of a receptor to produce multiple outputs) - offers a solution to thecross talk problem. In a minimal model we show that a single pleiotropicreceptor can simultaneously identify and accurately sense the concentrations ofarbitrary unknown ligands present individually or in a mixture. We calculatethe fundamental limits of the signaling specificity and accuracy of suchsignaling schemes. The model serves as an elementary "building block" towardsunderstanding more complex cross-wired receptor-ligand signaling networks.

Pleiotropy enables specific and accurate signaling in the presence of ligand cross talk