Hormone Metabolism, Biased Ligands and Complex Signaling

Traditional views of cell signaling often depict hormone perception mechanisms as simple on-off switches in a one-ligand-one-receptor model, wherein a particular receptor protein is activated solely by its pairing hormone with perfected binding kinetics. However, an increasing body of evidences suggests that hormone-receptor interactions in vivo are more sophisticated than previously thought, which may involve dynamic interactions between a series of structurally related hormone molecules and a family of divergent receptor proteins subject to spatial and temporal regulation. Hormone metabolism not only gives rise to the biosynthesis of one active hormone form, but also yield a series of related metabolites, including the precursor intermediates preceding hormone biosynthesis as well as the compounds that are further metabolized from the most commonly recognized active hormone form. Historically, the signaling properties of these additional hormone-related metabolites were at large overlooked without much scrutiny, yet some of these metabolites have indeed been exploited evolutionarily to serve as new signaling molecules, often in a “biased fashion”, contributing to the signaling complexity within the same organism or across divergent lineages. Using several classical phytohormone systems, we investigate the role of biased ligands, derived from evolutionarily elaborated hormone metabolic systems, in complex signaling regulation in plants.