Post-translational modification of receptors and signaling intermediates by protein tags regulates their functions. In the generic system depicted, a signal promotes conjugation of a tag to a target via an isopeptide bond between a lysine residue in the substrate and the C-terminus of the tag. A monomer or chain of tags might affect the stability of the target, its activity, its subcellular localization or its capacity to bind interacting partners. An antagonistic signal might reverse these functions by activating a protease that cleaves the tag from the substrate.