Regulation of mammalian Ste20 (Mst) kinases

• Mst1/Mst2/Hippo are core, conserved components of a tumor suppressor pathway.
• Mst/Hippo signaling has both similarities and key differences between mammals and flies.
• Homo- and heterodimerization play important roles in Mst regulation.

Initially identified as mammalian homologs to yeast Ste20 kinases, the mammalian sterile twenty-like (Mst) 1/2 kinases have been widely investigated subsequent to their rediscovery as key components of the Hippo tumor suppressor pathway in flies. To date, our understanding of Mst substrates and downstream signaling outstrips our knowledge of how these enzymes are controlled by upstream signals. While much remains to be discovered regarding the mechanisms of Mst regulation, it is clear that Mst1 kinase activity is governed at least in part by its state of dimerization, including self-association and also heterodimerization with various other signaling partners. Here we review the basic architecture of Mst signaling and function and discuss recent advances in our understanding of how these important kinases are regulated.