MST1/2 and Other Upstream Signaling that Affect Hippo Pathway Function

The Hippo signaling pathway is a conserved regulator of proliferation and cell survival in metazoans. The core of the pathway consists of a kinase cascade with the tumor suppressor Hippo (and its mammalian orthologues, MST1 and MST2) as the upstream kinase. Hippo activation is coupled to diverse stimuli, including cell contact, cell stress, and growth factor receptor signaling. These stimuli engage the Hippo pathway via multiple different signaling mechanisms that are cell type and cell context dependent. Notably, distinct mechanisms that control Hippo signaling have been uncovered in hematopoietic, epithelial, and mesenchymal lineages, and in cells exposed to strong inducers of apoptosis. Here we provide an overview of the signaling processes controlling mammalian Hippo pathway function, focusing on the direct regulation of MST1 and MST2 activity.