ArticleCell research2015
Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 142 citations in OpenAlex.
- Mechanobiology of the Hippo-YAP Signaling Network.Cold Spring Harbor perspectives in biology · 2026Article
- T-cell-targeted immunotherapy in neurofibromatosis type 2-related vestibular schwannoma: current evidence and future direction.Brain communications · 2026Review
- Article
- Gracillin suppresses cancer progression through inducing Merlin/LATS protein-protein interaction and activating Hippo signaling pathway.Acta pharmacologica Sinica · 2025Article
- The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.Cell reports · 2025Article
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- The Hippo Pathway in Breast Cancer: The Extracellular Matrix and Hypoxia.International journal of molecular sciences · 2024Review
- Review
- MerlinNature communications · 2024Article
- FERM domain-containing proteins are active components of the cell nucleus.Life science alliance · 2024Review
- Retinoic acid induced specific changes in the phosphoproteome of C17.2 neural stem cells.Journal of cellular and molecular medicine · 2024Article
- Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future.Cell biology and toxicology · 2024Review
- Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Development of Novel Bioluminescent Biosensors Monitoring the Conformation and Activity of the Merlin Tumour Suppressor.International journal of molecular sciences · 2024Article
- Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential.Analytical cellular pathology (Amsterdam) · 2024Review
- PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.International journal of molecular sciences · 2023Article
- Missense variant interaction scanning reveals a critical role of the FERM domain for tumor suppressor protein NF2 conformation and function.Life science alliance · 2023Article
- The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment.Cancers · 2023Review
- Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion.Cells · 2023Article
- Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.Cell communication and signaling : CCS · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Lats1/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase CRL4(DCAF1). Numerous mutations of Merlin have been identified in Neurofibromatosis type 2 and other cancer patients. Despite more than two decades of research, the upstream regulator of Merlin in the Hippo pathway remains unknown. Here we show by high-resolution crystal structures that the Lats1/2-binding site on the Merlin FERM domain is physically blocked by Merlin's auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and promotes Merlin's binding to Lats1/2. Phosphorylation of Ser518 outside the Merlin's auto-inhibitory tail does not obviously alter Merlin's conformation, but instead prevents angiomotin from binding and thus inhibits Hippo pathway kinase activation. Cancer-causing mutations clustered in the angiomotin-binding domain impair angiomotin-mediated Merlin activation. Our findings reveal that angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling, and allow construction of a complete Hippo signaling pathway.
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Registered trials
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.