Hippo and PI5P4K signaling intersect to control the transcriptional activation of YAP.
| Publication Type | Academic Article |
| Authors | Palamiuc L, Johnson J, Haratipour Z, Loughran R, Choi W, Arora G, Tieu V, Ly K, Llorente A, Crabtree S, Wong J, Ravi A, Wiederhold T, Murad R, Blind R, Emerling B |
| Journal | Sci Signal |
| Volume | 17 |
| Issue | 838 |
| Pagination | eado6266 |
| Date Published | 05/28/2024 |
| ISSN | 1937-9145 |
| Keywords | Protein Serine-Threonine Kinases, Signal Transduction, Hippo Signaling Pathway, Adaptor Proteins, Signal Transducing, Transcription Factors, YAP-Signaling Proteins |
| Abstract | Phosphoinositides are essential signaling molecules. The PI5P4K family of phosphoinositide kinases and their substrates and products, PI5P and PI4,5P2, respectively, are emerging as intracellular metabolic and stress sensors. We performed an unbiased screen to investigate the signals that these kinases relay and the specific upstream regulators controlling this signaling node. We found that the core Hippo pathway kinases MST1/2 phosphorylated PI5P4Ks and inhibited their signaling in vitro and in cells. We further showed that PI5P4K activity regulated several Hippo- and YAP-related phenotypes, specifically decreasing the interaction between the key Hippo proteins MOB1 and LATS and stimulating the YAP-mediated genetic program governing epithelial-to-mesenchymal transition. Mechanistically, we showed that PI5P interacted with MOB1 and enhanced its interaction with LATS, thereby providing a signaling connection between the Hippo pathway and PI5P4Ks. These findings reveal how these two important evolutionarily conserved signaling pathways are integrated to regulate metazoan development and human disease. |
| DOI | 10.1126/scisignal.ado6266 |
| PubMed ID | 38805583 |
| PubMed Central ID | PMC11283293 |