Proofreading does not result in more reliable ligand discrimination in receptor signaling due to its inherent stochasticity.

Kinetic proofreading (KPR) has been used as a paradigmatic explanation for the high specificity of ligand discrimination by cellular receptors. KPR enhances the difference in the mean receptor occupancy between different ligands compared to a nonproofread receptor, thus potentially enabling better discrimination. On the other hand, proofreading also attenuates the signal and introduces additional stochastic receptor transitions relative to a nonproofreading receptor.

Determinants of Ligand Specificity and Functional Plasticity in Type I Interferon Signaling.

The Type I Interferon family of cytokines all act through the same cell surface receptor and induce phosphorylation of the same subset of response regulators of the STAT family. Despite their shared receptor, different Type I Interferons have different functions during immune response to infection. In particular, they differ in the potency of their induced anti-viral and anti-proliferative responses in target cells.

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

Living cells sense their environment through the binding of extracellular molecular ligands to cell surface receptors. Puzzlingly, vast numbers of signaling pathways exhibit a high degree of cross talk between different signals whereby different ligands act through the same receptor or shared components downstream. It remains unclear how a cell can accurately process information from the environment in such cross-wired pathways.