ArticleThe Journal of biological chemistry2015
Phosphorylation of the Hippo Pathway Component AMOTL2 by the mTORC2 Kinase Promotes YAP Signaling, Resulting in Enhanced Glioblastoma Growth and Invasiveness.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 92 citations in OpenAlex.
- AMOTL2 inhibits lymph node metastasis in gastric cancer by suppressing TGF-β/Smad signaling and is destabilized by the E3 ubiquitin ligase SMURF1.International journal of biological sciences · 2026Article
- Phosphorylation of tumour suppressor Amotl2 by IKBKE kinase promotes YAP1 signalling, enhancing glioblastoma growth.Frontiers in oncology · 2026Article
- Proteomic Exploration of L1CAMInternational journal of molecular sciences · 2025Article
- Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures.Molecular systems biology · 2025Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway.Cell death & disease · 2024Article
- Targeting the Hippo pathway to prevent radioresistance brain metastases from the lung (Review).International journal of oncology · 2024Review
- Role of angiomotin family members in human diseases (Review).Experimental and therapeutic medicine · 2024Review
- Integrated clinical and prognostic analyses of mTOR/Hippo pathway core genes in hepatocellular carcinoma.Journal of physiology and biochemistry · 2024Article
- Regulation of YAP Promotor Accessibility in Endothelial Mechanotransduction.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Regulation of CD8Cellular & molecular immunology · 2023Review
- ZNF143 facilitates the growth and migration of glioma cells by regulating KPNA2-mediated Hippo signalling.Scientific reports · 2023Article
- In Situ Nitric Oxide Gas Nanogenerator Reprograms Glioma Immunosuppressive Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- The Hippo signaling pathway: from multiple signals to the hallmarks of cancers.Acta biochimica et biophysica Sinica · 2023Review
- CircAMOTL1 RNA and AMOTL1 Protein: Complex Functions ofInternational journal of molecular sciences · 2023Review
- The mammalian target of rapamycin contributes to synovial fibroblast pathogenicity in rheumatoid arthritis.Frontiers in medicine · 2023Article
- Anti-invasive efficacy and survival benefit of the YAP-TEAD inhibitor verteporfin in preclinical glioblastoma models.Neuro-oncology · 2022Article
- mTOR Signaling Components in Tumor Mechanobiology.International journal of molecular sciences · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) and Hippo signaling pathways are two major signaling cascades that coordinately regulate cell growth and proliferation. Dysregulation of these pathways plays a critical role in gliomagenesis. Recent reports have provided evidence of cross-talk between the mTOR and Hippo pathways; however, a complete description of the signaling relationships between these pathways remains to be elucidated. Utilizing a gene-trapping strategy in a mouse glioma model, we report the identification of AMOTL2 as a candidate substrate for mTORC2. AMOTL2 is phosphorylated at serine 760 by mTORC2. Mutation of AMOTL2 mimicking constitutive Ser(760) phosphorylation blocks its ability to bind and repress YAP leading to increased relative expression of known YAP gene targets. Moreover, overexpression of AMOTL2 or a nonphosphorylatable AMOTL2-S760A mutant inhibited YAP-induced transcription, foci formation, growth, and metastatic properties, whereas overexpression of a phosphomimetic AMOTL2-S760E mutant negated these repressive effects of AMOTL2 in glioblastoma (GBM) cells in vitro. Similar effects on xenograft growth were observed in GBM cells expressing these AMOTL2 Ser(760) mutants. YAP was also shown to be required for Rictor-mediated GBM growth and survival. Finally, an analysis of mTORC2/AMOTL2/YAP activities in primary GBM samples supported the clinical relevance of this signaling cascade, and we propose that pharmacological agents cotargeting these regulatory circuits may hold therapeutic potential.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.