The Mst1/2 kinases are cytosolic Ste20-related kinases activated by autophosphorylation. Designated class II GC kinases, Mst1 and Mst2, share 76% sequence identity and contain an N-terminal catalytic domain, followed successively by an autoinhibitory segment and a coiled-coil SARAH domain that mediates hetero- and homo-dimerisation. Mst1 and Mst2 also become activated in cells undergoing apoptosis from a variety of stimuli. The activation mechanism is unclear, however, once activated, both kinases undergo cleavage by caspase3 at sites just carboxy terminal to their catalytic domains. The resultant catalytic polypeptides display an altered substrate specificity and lack their autoinhibitory domain. The caspase-cleaved catalytic fragments are highly and constitutively active with unrestricted nuclear access.