PMID: 26108669 RLIMS-P 4 eFIP 2 miRTex 0 eGARD 0 Issue Report
Title
| 1. | Structural basis for Mob1-dependent activation of the core Mst-Lats kinase cascade in Hippo signaling. |
Abstract
| 2. | The Mst-Lats kinase cascade is central to the Hippo tumor-suppressive pathway that controls organ size and tissue homeostasis. |
| 3. | The adaptor protein Mob1 promotes Lats activation by Mst, but the mechanism remains unknown. |
| 4. | Here, we show that human Mob1 binds to autophosphorylated docking motifs in active Mst2. |
| 5. | This binding enables Mob1 phosphorylation by Mst2. |
| 6. | Phosphorylated Mob1 undergoes conformational activation and binds to Lats1. |
| 7. | We determine the crystal structures of phospho-Mst2-Mob1 and phospho-Mob1-Lats1 complexes, revealing the structural basis of both phosphorylation-dependent binding events. |
| 8. | Further biochemical and functional analyses demonstrate that Mob1 mediates Lats1 activation through dynamic scaffolding and allosteric mechanisms. |
| 9. | Thus, Mob1 acts as a phosphorylation-regulated coupler of kinase activation by virtue of its ability to engage multiple ligands. |
| 10. | We propose that stepwise, phosphorylation-triggered docking interactions of nonkinase elements enhance the specificity and robustness of kinase signaling cascades. |
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