While the original Y2H system used a reconstituted transcription factor, other systems create enzymatic activities to detect PPIs. For instance, the KInase Substrate Sensor ("KISS"), is a mammalian two-hybrid approach has been designed to map intracellular PPIs. Here, a bait protein  is fused to a kinase-containing portion of TYK2 and a prey is coupled to a gp130 cytokine receptor fragment. When bait and prey interact, TYK2 phosphorylates STAT3 docking sites on the prey chimera, which ultimately leads to activation of a reporter gene.