Figure 5.
Alterations in the mammalian Hippo signaling pathway alter FLNA phosphorylation. A schematic depicting the potential link between the Hippo signaling pathway and FLNA phosphorylation as outlined in this study. MST1/2 kinases (also known as “Hippo”), activated by FAT4/DCHS1, induces phosphorylation of YAP and NDR kinases. Phosphorylation of YAP leads to its degradation in the cytoplasm, while reduced activity of MST (e.g., via loss of DCHS1 activity) attenuates YAP phosphorylation and results in its translocation in the nucleus where it promotes changes to transcription. Phosphorylation of NDR1/2 facilitates its kinase activity. NDR1/2 kinases are further modulated by MOB1 (not shown) and MOB2 either positively or negatively, respectively. NDR1/2 kinases regulate the phosphorylation of the MEKK family of proteins, known modulators of FLNA phosphorylation (at site Ser2152) and activity. In addition to disrupting nucleus-cilia coupling, reduced levels of MOB2 where seen in this study to induce changes in FLNA phosphorylation. A feature which could be mediated by the MEKK kinases given the associated supporting information.