A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis
| Autor: | Audrey Champagne, Christopher J. Nicol, Kun-Liang Guan, Frédéric Pouliot, Bertrand Neveu, Elizabeth Lightbody, Yawei Hao, B. Yeung, Jianmin Zhang, V. R. Kay, H. J. Janse van Rensburg, B. A. Croy, Taha Azad, Xiaolong Yang, Abdi Ghaffari, He Shen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Angiogenesis Regulator General Physics and Astronomy Biosensing Techniques Cardiovascular Phosphatidylinositol 3-Kinases Receptors Site-Directed lcsh:Science Multidisciplinary Blotting Kinase Chemistry Vascular Endothelial Growth Factor Adaptor Proteins Signal transducing adaptor protein Protein-Serine-Threonine Kinases Immunohistochemistry Cell biology Hippo signaling Female Western Biotechnology Signal Transduction endocrine system animal structures 1.1 Normal biological development and functioning Science Blotting Western Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Underpinning research Animals Humans Vasculogenic mimicry PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Hippo signaling pathway Tumor Suppressor Proteins fungi Signal Transducing General Chemistry Phosphoproteins body regions 030104 developmental biology HEK293 Cells Receptors Vascular Endothelial Growth Factor Mutagenesis A549 Cells Mutagenesis Site-Directed lcsh:Q sense organs Transcription Factors |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018) Nature Communications Nature communications, vol 9, iss 1 |
| ISSN: | 2041-1723 |
| Popis: | The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings. The Hippo pathway is a major orchestrator of organ development and homeostasis. Here Azad and colleagues develop a biosensor to monitor the activity of the Hippo pathway component LATS and identify VEGF signalling as an upstream regulator of LATS, supporting a role for Hippo signalling during angiogenesis. |
| Databáze: | OpenAIRE |
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