PMC

Figure 1. A schematic of MST1/2 and KrsB signaling in mammalian and D. discoideum cells. (A) Canonical pathway regulating growth. Activated MST1/2 kinase interacts with Sav1 to phosphorylate Mob1 and LATS1/2 kinase, which work together to phosphorylate a transcriptional coactivator YAP, leading to its retention in the cytoplasm. Unphosphorylated YAP translocates to the nucleus, where, together with TEAD, it drives transcription of various genes important for cell proliferation and survival. For simplicity the schematic does not include upstream regulators of MST1/2. (B) Emerging pathways regulating cell morphology in T-lymphocytes and D. discoideum. In T-lymphocytes T cell receptor (TCR) ligation or stimulation with chemokines leads to MST1 activation downstream of Rap1 and its binding partner RAPL. Active MST1 promotes cell polarization, substrate adhesion and migration in part by inducing LFA-1 clustering. Whether MST1 functions independently of transcription in T cells is unclear. In Dictyostelium stimulation with a chemoattractant cAMP triggers transient activation of KrsB in a G-protein-dependent and PI3K- and TORC2-independent manner. In contrast to T cells, active KrsB negatively regulates cell substrate adhesion in part due to changes in the cytoskeleton. Solid lines with arrows and blunted ends refer to positive and inhibitory actions, respectively. Dotted arrows indicate less well-characterized pathways.