Affinage

AMOTL2

Angiomotin-like protein 2 · UniProt Q9Y2J4

Length
779 aa
Mass
85.8 kDa
Annotated
2026-06-09
31 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AMOTL2 is a junctional scaffold protein that mechanically couples cadherin-based cell-cell junctions to the contractile actin cytoskeleton and the nuclear lamina, and acts as a regulatory hub for the Hippo and Wnt pathways governing cell shape, polarity, and proliferation (PMID:24806444, PMID:28842668, PMID:39195920). At adherens junctions, the p100 AMOTL2 isoform forms complexes with VE-cadherin or E-cadherin that organize radial actin filaments, transmitting extracellular mechanical force through to the nuclear membrane; this coupling requires Par3 for junctional localization and drives lumen expansion, epithelial packing geometry, blastocyst hatching, and flow-induced endothelial alignment, with its loss in endothelium producing pro-inflammatory aortic aneurysm phenotypes (PMID:24806444, PMID:28790366, PMID:28842668, PMID:39195920). AMOTL2 represses the transcriptional co-activators YAP/TAZ: it binds TAZ through a PPXY-WW interaction to control its nuclear translocation (PMID:23911299), and WWP1-mediated mono-ubiquitination at K347/K408 enables AMOTL2 to recruit LATS2 and SAV1 to promote YAP phosphorylation and cytoplasmic sequestration under high cell density (PMID:34404733), while it also stabilizes LATS1/2 to sustain YAP repression (PMID:38956029). This YAP-repressive activity is switched off by mTORC2 phosphorylation at S760 and by CLK2-dependent alternative splicing that yields a membrane-uncoupled isoform (PMID:25998128, PMID:38126343). AMOTL2 additionally attenuates Wnt signaling by trapping β-catenin in Rab11-positive recycling endosomes (PMID:22362771, PMID:34036399), and a hypoxia-induced p60 isoform sequesters Crb3/Par3 polarity complexes and uncouples p100 AMOTL2 from the actin-nuclear lamina axis to promote tumor invasion (PMID:25080976, PMID:37443716). Through c-Src binding it facilitates membrane translocation and MAPK/ERK activation (PMID:17293535, PMID:21937427), and it modulates STAT1-dependent type I interferon signaling to restrict Zika virus replication (PMID:40892926).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2007 Medium

    Established the first cellular role for Amotl2 by linking it to active c-Src and cytoskeletal/membrane organization during morphogenetic cell movements.

    Evidence Zebrafish morpholino knockdown, mosaic transplantation, and co-IP with phospho-c-Src and endosomal markers

    PMID:17293535

    Open questions at the time
    • Direct binding interface with c-Src not mapped
    • Did not connect c-Src translocation to a specific downstream signaling output
  2. 2011 High

    Defined a tyrosine-103-dependent, PDZ-independent mechanism by which Amotl2 drives c-Src-mediated MAPK/ERK activation in endothelial morphogenesis.

    Evidence HUVEC siRNA, Y103 site-directed mutagenesis, ERK assays, and zebrafish vessel-growth readouts

    PMID:21937427

    Open questions at the time
    • How Y103 phosphorylation is regulated upstream unknown
    • Relationship of ERK arm to junctional/Hippo functions not integrated
  3. 2012 High

    Showed Amotl2 restrains Wnt signaling by physically trapping β-catenin in recycling endosomes rather than acting at the destruction complex.

    Evidence Zebrafish epistasis with axin1 mutant, co-IP, and Rab11 endosome co-localization

    PMID:22362771

    Open questions at the time
    • Determinants of β-catenin capture vs release not defined
    • Whether endosomal sequestration is regulated by signaling unknown
  4. 2013 Medium

    Identified AMOTL2 as a direct, Hippo-independent regulator of TAZ nuclear translocation via a PPXY-WW interaction, foreshadowing its central role over YAP/TAZ.

    Evidence Co-IP with domain mutagenesis (PPXY), luciferase reporter, and overexpression in H441 lung cells

    PMID:23911299

    Open questions at the time
    • Single cell type
    • Did not reconcile Hippo-independent claim with later LATS-dependent mechanism
  5. 2013 Medium

    Placed Amotl2 at specialized actin-based adhesion structures (synaptic podosomes, invadopodia) through interaction with the scaffold LL5β.

    Evidence Affinity purification/MS, co-IP, and siRNA knockdown with morphometric analysis in myotubes and fibroblasts

    PMID:23525008

    Open questions at the time
    • Mechanism linking LL5β binding to podosome size unknown
    • Not connected to cadherin/Hippo functions
  6. 2014 High

    Demonstrated that AmotL2 mechanically couples VE-cadherin junctions to contractile actin to generate the tensile forces required for vascular lumen expansion.

    Evidence Zebrafish/mouse inactivation, endothelial co-IP with VE-cadherin complex, and traction force microscopy

    PMID:24806444

    Open questions at the time
    • Direct actin-binding interface not resolved
    • How force is sensed/transduced not yet defined
  7. 2014 High

    Revealed isoform-specific control whereby a hypoxia-induced p60 AmotL2 sequesters Crb3/Par3 polarity complexes to disrupt apical-basal polarity and drive invasion.

    Evidence c-Fos promoter analysis, co-IP with polarity complexes, vesicle trafficking assays, and xenograft

    PMID:25080976

    Open questions at the time
    • Isoform-specific structural basis for polarity-complex retention unknown
    • p60 vs p100 abundance control incompletely defined
  8. 2015 High

    Identified mTORC2-dependent S760 phosphorylation as an off-switch for AMOTL2's YAP-repressive function, linking growth signaling to Hippo output.

    Evidence Mouse glioma gene-trap, S760A/S760E mutagenesis, co-IP with YAP, and xenograft tumor assays

    PMID:25998128

    Open questions at the time
    • How S760 phosphorylation alters AMOTL2-YAP binding structurally unknown
    • Other mTORC2 substrates in the axis not addressed
  9. 2017 Medium

    Established Par3 as the localization determinant placing AmotL2 at junctions to build the cadherin-actin axis controlling tissue geometry.

    Evidence Zebrafish inactivation, cell-culture siRNA, immunofluorescence, and co-IP

    PMID:28790366

    Open questions at the time
    • Direct vs indirect Par3-AmotL2 interaction not distinguished
    • Single lab
  10. 2017 High

    Showed the p100 isoform forms an E-cadherin/radial-actin complex that generates the contractile tension required for blastocyst hatching and epithelial packing.

    Evidence Co-IP, zebrafish/mouse inactivation, and blebbistatin phenocopy of myosin-II loss

    PMID:28842668

    Open questions at the time
    • Stoichiometry of E-cadherin/AmotL2/actin complex unresolved
    • Quantitative force contribution not measured
  11. 2020 High

    Uncovered a junction-independent role for AMOTL2 in sequestering the PP2A subunit PPP2R2A in the cytoplasm to sustain phospho-JUN and AP-1 proliferation signaling.

    Evidence CRISPR loss-of-function screen, MS, co-IP/GST pull-down, fractionation, and phospho-JUN immunoblot in NSCLC

    PMID:32950569

    Open questions at the time
    • Whether PPP2R2A binding competes with YAP/cadherin functions unknown
    • Regulation of this interaction not defined
  12. 2021 High

    Defined WWP1-mediated mono-ubiquitination at K347/K408 as the molecular trigger that enables AMOTL2 to recruit LATS2/SAV1 and drive YAP phosphorylation at high cell density.

    Evidence In vitro ubiquitination, K347/K408 mutagenesis, co-IP with LATS2/SAV1, and contact-inhibition assays

    PMID:34404733

    Open questions at the time
    • Deubiquitinase counteracting WWP1 not identified
    • How Crumbs coupling is regulated mechanistically unresolved
  13. 2021 Medium

    Extended the β-catenin sequestration mechanism to glioma, showing AMOTL2 loss enhances Wnt-driven proliferation and invasion.

    Evidence Co-IP, immunofluorescence, and siRNA knockdown in glioma cell lines

    PMID:34036399

    Open questions at the time
    • Single lab, no in vivo validation
    • Did not test endosomal trapping specifically
  14. 2021 Medium

    Placed AMOTL2 downstream of MAGI1 loss as an upstream driver of a ROCK/p38 stress pathway in breast cancer.

    Evidence Double-knockdown epistasis, ROCK/p38 inhibitor rescue, and cell-stiffness/tumorigenicity assays

    PMID:33707576

    Open questions at the time
    • Direct molecular link from AMOTL2 to ROCK/p38 not shown
    • In vitro only
  15. 2021 Medium

    Confirmed AMOTL2 restrains TGF-β1-induced YAP1 activation in airway smooth muscle, linking it to proliferation and ECM deposition.

    Evidence Overexpression/knockdown in ASM cells with YAP1 nuclear-localization and constitutively-active YAP1 rescue

    PMID:34323359

    Open questions at the time
    • No direct AMOTL2-YAP1 binding assay reported
    • Single lab
  16. 2022 Low

    Showed AMOTL2 is transcriptionally repressed by MEF2D, derepressing YAP signaling to promote hepatocellular carcinoma.

    Evidence Dual luciferase reporter and overexpression in hepatoma cells

    PMID:35698637

    Open questions at the time
    • Limited mechanistic depth; promoter binding inferred
    • No in vivo confirmation
  17. 2023 Medium

    Identified CLK2-dependent alternative splicing as a regulator that generates a membrane-uncoupled AMOTL2 isoform, switching off YAP repression.

    Evidence Chemical screen, RT-PCR splicing analysis, and YAP phosphorylation/localization assays with CLK2 inhibitor

    PMID:38126343

    Open questions at the time
    • Spliced isoform binding partners not reconstituted
    • Physiological context of CLK2 control unclear
  18. 2023 Medium

    Revealed the mechanism of p60-driven invasion: p60 binds p100 AMOTL2 to uncouple E-cadherin-radial actin from the nuclear lamina, softening the nucleus for ameboid migration.

    Evidence Inter-isoform co-IP, atomic force microscopy of nuclear stiffness, and micropore invasion assays

    PMID:37443716

    Open questions at the time
    • Direct nuclear-lamina binding partner not identified
    • Single lab
  19. 2023 High

    Demonstrated in vivo that AmotL2 transmits flow-derived mechanical signals from VE-cadherin junctions through actin to the nuclear lamina, with endothelial loss causing aortic aneurysms.

    Evidence Endothelial-specific mouse knockout, tripartite co-IP, nuclear-lamina connectivity assays, and transcriptomics

    PMID:39195920

    Open questions at the time
    • Identity of the nuclear-lamina anchoring partner unresolved
    • Mechanotransduction signaling steps to inflammation not fully mapped
  20. 2024 Medium

    Identified ARNTL2 as a transcriptional repressor of AMOTL2 that, by reducing LATS1/2 recruitment and stabilization, activates YAP to promote nasopharyngeal carcinoma invasion.

    Evidence ChIP, knockdown epistasis with rescue, LATS1/2 co-IP, and xenograft

    PMID:38956029

    Open questions at the time
    • Direct LATS1/2 stabilization mechanism vs recruitment not separated
    • Single lab
  21. 2024 Low

    Positioned AMOTL2 as a mediator in a WBP2/c-JUN chemoresistance axis in breast cancer.

    Evidence RNA-seq, knockdown epistasis, phospho-c-JUN immunoblot, and xenograft with MG132

    PMID:39709035

    Open questions at the time
    • No direct AMOTL2/c-JUN binding assay
    • Mechanism of drug-resistance protein induction unclear
  22. 2025 Medium

    Identified AMOTL2 as a direct binding target of the natural product celastrol, linking pharmacological engagement to Hippo activation and cardiomyocyte apoptosis.

    Evidence Activity-based protein profiling, shRNA knockdown rescue, YAP1 phosphorylation and mitochondrial biogenesis assays, and mouse cardiotoxicity model

    PMID:41412440

    Open questions at the time
    • Celastrol binding site on AMOTL2 not mapped
    • Whether binding mimics a physiological regulatory event unknown
  23. 2025 Medium

    Uncovered an antiviral role in which AMOTL2 promotes the type I interferon response by modulating STAT1 to restrict Zika virus replication.

    Evidence Genome-wide CRISPR knockout screen for ZIKV host factors with STAT1 activation and ISG expression follow-up

    PMID:40892926

    Open questions at the time
    • Direct molecular interaction with STAT1 not demonstrated
    • Relation to junctional/Hippo roles unknown
  24. 2025 Medium

    Showed AmotL2 and Yap1 form an opposing mechanosensitive module balancing actomyosin tension to enable flow-guided vascular pruning.

    Evidence Zebrafish live imaging, amotL2/yap1 genetic analysis, and actomyosin tension measurements (preprint)

    PMID:bio_10.1101_2025.11.19.689183

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Molecular basis of the AmotL2-Yap1 balance during pruning not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis by which AMOTL2 physically bridges cadherin, actin, and the nuclear lamina, and how its multiple regulatory inputs (ubiquitination, phosphorylation, splicing, isoform balance, transcriptional repression) are integrated within a single cell, remains unresolved.
  • No structural model of AMOTL2 complexes
  • Nuclear-lamina anchoring partner unidentified
  • Cross-talk between Hippo, Wnt, MAPK, and interferon roles not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0140313 molecular sequestering activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005635 nuclear envelope 2 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 1
Partners
CDH1CDH5CTNNB1LATS2PARD3PPP2R2ATAZ/WWTR1YAP1
Complex memberships
E-cadherin/p100-AMOTL2/radial actin complexLATS2/SAV1 Hippo complexVE-cadherin adherens junction complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Amotl2 interacts preferentially with phosphorylated c-Src and facilitates its outward translocation to the membrane, regulating membrane architecture and F-actin organization; knockdown of amotl2 in zebrafish delays epiboly and impairs convergence/extension cell movements, and amotl2-deficient cells fail to migrate properly with loss of membrane protrusions. Zebrafish morpholino knockdown, mosaic transplantation, co-immunoprecipitation, co-localization with endosomal markers (RhoB, EEA1) Development (Cambridge, England) Medium 17293535
2011 Amotl2 promotes MAPK/ERK activation via c-Src in endothelial cells, dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain; knockdown impairs endothelial cell proliferation, migration, polarity, and tube formation in vitro, and intersegmental vessel growth in zebrafish. Zebrafish transgenic line knockdown, HUVEC siRNA knockdown, site-directed mutagenesis (Y103), ERK activity assays, cell polarity and tube formation assays The Journal of biological chemistry High 21937427
2012 Amotl2 attenuates Wnt/β-catenin signaling by associating with and trapping β-catenin in Rab11-positive recycling endosomes, reducing the amount of β-catenin available in the cytosol and nucleus; knockdown in zebrafish causes embryonic dorsalization rescued by co-knockdown of β-catenin2. Zebrafish morpholino knockdown, genetic epistasis with axin1 mutant (masterblind), co-immunoprecipitation, immunofluorescence with Rab11 co-localization in mammalian cells The Journal of biological chemistry High 22362771
2013 AMOTL2 co-immunoprecipitates with TAZ via the WW domain of TAZ and the PPXY motif in the N-terminus of AMOTL2; AMOTL2 co-localizes with TAZ in the cytoplasm and regulates TAZ cytoplasm-to-nucleus translocation through direct protein-protein interaction, inhibiting TAZ-dependent transcription of surfactant genes in lung cells in a Hippo-independent manner. Co-immunoprecipitation, immunofluorescence co-localization, luciferase reporter assay, domain mutagenesis (PPXY motif), overexpression in H441 lung cells Gene Medium 23911299
2013 Amotl2 interacts with the scaffold protein LL5β at synaptic podosomes in myotubes and neuromuscular junctions in vivo; depletion of Amotl2 in myotubes increases size of synaptic podosomes and alters postsynaptic topology, and depletion in fibroblasts disrupts invadopodia. Affinity purification/mass spectrometry (LL5β-associated proteins), co-immunoprecipitation, immunofluorescence in vivo and in vitro, siRNA knockdown with morphometric analysis Journal of cell science Medium 23525008
2014 AmotL2 associates with the VE-cadherin adherens junction complex and couples it to contractile actin fibres; inactivation of amotL2 in zebrafish, mouse, and endothelial cell culture dissociates VE-cadherin from cytoskeletal tensile forces, impairing aortic vessel lumen expansion. Gene inactivation in zebrafish and mouse, endothelial cell culture knockdown, co-immunoprecipitation with VE-cadherin complex, traction force microscopy, live imaging Nature communications High 24806444
2014 Hypoxic stress induces c-Fos-dependent expression of a p60 AmotL2 isoform; p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes, retaining them in large vesicles and preventing them from reaching the apical membrane, causing loss of apical-basal polarity and promoting tumor invasion. Immunoprecipitation, immunofluorescence, siRNA knockdown in vitro, mouse xenograft in vivo, c-Fos promoter analysis, vesicle trafficking assays Nature communications High 25080976
2015 mTORC2 phosphorylates AMOTL2 at serine 760; phosphomimetic S760E mutation blocks AMOTL2's ability to bind and repress YAP, increasing YAP target gene expression, foci formation, and metastatic properties, whereas non-phosphorylatable S760A mutant retains YAP repression activity in glioblastoma cells and xenografts. Gene-trap in mouse glioma model, phosphosite mutagenesis (S760A/S760E), co-immunoprecipitation with YAP, YAP transcriptional reporter assays, foci formation assay, xenograft tumor growth The Journal of biological chemistry High 25998128
2017 Par3 is essential for localization of AmotL2 to cellular junctions, where it associates with VE/E-cadherin to organize radial actin filaments; loss of this Par3-AmotL2-cadherin-actin axis impairs aortic lumen expansion and epithelial hexagonal packing. Gene inactivation in zebrafish, siRNA knockdown in cell culture, immunofluorescence, co-immunoprecipitation Scientific reports Medium 28790366
2017 p100 AmotL2 forms a complex with E-cadherin that associates with radial actin filaments connecting cells across multiple layers; genetic inactivation of amotL2 leads to loss of contractile actin filaments and perturbed epithelial packing geometry; amotL2 is required for blastocyst hatching in mouse and zebrafish via tension generation, phenocopied by myosin II inhibitor blebbistatin. Co-immunoprecipitation, zebrafish and mouse genetic inactivation, immunofluorescence, blebbistatin pharmacological inhibition, blastocyst hatching assay Scientific reports High 28842668
2020 AMOTL2 is a binding partner of PPP2R2A (a PP2A regulatory subunit) in NSCLC cells; AMOTL2 binds PPP2R2A in the cytoplasm, reducing its nuclear localization and thereby preventing PPP2R2A-mediated dephosphorylation of JUN at Thr239, which suppresses AP-1-driven cell proliferation. CRISPR/Cas9 loss-of-function screen, mass spectrometry, co-immunoprecipitation, GST pull-down, immunofluorescence, subcellular fractionation, phospho-JUN immunoblotting Biochimica et biophysica acta. Molecular cell research High 32950569
2021 E3 ubiquitin ligase WWP1 mono-ubiquitinates AMOTL2 at K347 and K408; mono-ubiquitinated AMOTL2 interacts with LATS2 and facilitates recruitment of SAV1, promoting YAP phosphorylation and cytoplasmic sequestration/degradation; this process is coupled to Crumbs polarity complex at cell junctions under high cell density conditions. In vitro ubiquitination assay, ubiquitination site mutagenesis (K347/K408), co-immunoprecipitation with LATS2/SAV1, YAP phosphorylation immunoblotting, cell density contact inhibition assays, immunofluorescence Life science alliance High 34404733
2021 AMOTL2 directly binds β-catenin and regulates its nuclear translocation in glioma cells; knockdown of AMOTL2 promotes β-catenin nuclear localization and downstream Wnt target gene expression, enhancing glioma proliferation, migration, and invasion. Co-immunoprecipitation, immunofluorescence, immunoblotting, siRNA knockdown in glioma cell lines Oncology reports Medium 34036399
2021 Loss of MAGI1 causes accumulation of E-cadherin and AMOTL2 and increased ROCK and p38 SAPK activities; rescue experiments show that AMOTL2 depletion or p38 inhibition reverses the increased tumorigenicity of MAGI1-deficient cells, placing AMOTL2 upstream of a ROCK/p38 stress pathway in luminal breast cancer. Genetic epistasis (double knockdown), ROCK/p38 inhibitor pharmacology, cell stiffness measurement, tumorigenicity assays in vitro Scientific reports Medium 33707576
2021 AMOTL2 restrains YAP1 activation in airway smooth muscle cells; overexpression of AMOTL2 suppresses TGF-β1-induced YAP1 nuclear translocation, and reactivation of YAP1 reverses AMOTL2-mediated suppression of proliferation and ECM deposition. Overexpression and siRNA knockdown in ASM cells, YAP1 nuclear localization assay, proliferation and ECM deposition functional assays, rescue with constitutively active YAP1 Environmental toxicology Medium 34323359
2022 MEF2D binds the MEF2 cis-acting element in the upstream promoter region of AMOTL2, inhibiting its transcriptional expression, thereby activating YAP signaling and promoting HCC cell migration and proliferation. Dual luciferase reporter assay, ChIP (implied by promoter binding), overexpression experiments in hepatoma cells International journal of clinical and experimental pathology Low 35698637
2023 CLK2 inhibition promotes alternative splicing of AMOTL2 producing an exon-skipped isoform that can no longer associate with membrane-bound proteins, resulting in decreased YAP phosphorylation and decreased membrane localization of YAP, thereby activating YAP-driven transcription. High-throughput chemical screen, RT-PCR for alternative splicing, YAP phosphorylation and localization assays, CLK2 inhibitor (SM04690) pharmacology eLife Medium 38126343
2023 p60 AmotL2 (expressed in invading tumor cells) binds to the p100 AmotL2 isoform and uncouples the mechanical constraint of radial actin filaments from E-cadherin; the E-cadherin/p100AmotL2 complex is directly connected to the nuclear membrane, and p60AmotL2 expression inactivates this connection, altering nuclear lamina properties and potentiating ameboid invasion through extracellular matrix micropores. Co-immunoprecipitation between isoforms, nuclear lamina connectivity assays, atomic force microscopy, micropore invasion assays, overexpression/knockdown in tumor cell lines Cells Medium 37443716
2023 AmotL2 connects junctional VE-cadherin and actin filaments to the nuclear lamina in endothelial cells; AmotL2 is essential for radial actin filament formation and endothelial cell alignment in response to blood flow; loss of endothelial AmotL2 in mice causes a pro-inflammatory response and abdominal aortic aneurysms. Molecular analysis showed VE-cadherin binds AmotL2 and actin, transmitting extracellular mechanical signals to the nuclear membrane. Endothelial-specific mouse knockout, co-immunoprecipitation (VE-cadherin/AmotL2/actin), immunofluorescence for nuclear lamina connectivity, transcriptome analysis, live imaging Nature cardiovascular research High 39195920
2024 ARNTL2 negatively regulates AMOTL2 transcription by directly binding to the AMOTL2 promoter; reduced AMOTL2 decreases its recruitment and stabilization of LATS1/2 kinases, reducing LATS-dependent YAP phosphorylation and promoting YAP nuclear translocation and NPC invasion; inhibition of AMOTL2 counteracted the effect of ARNTL2 knockdown. ChIP (ARNTL2 binding to AMOTL2 promoter), siRNA/shRNA knockdown epistasis, LATS1/2 co-immunoprecipitation with AMOTL2, YAP phosphorylation and localization assays, xenograft mouse model Cell death & disease Medium 38956029
2024 WBP2 overexpression activates AMOTL2 and nuclear phosphorylated c-JUN in breast cancer cells; AMOTL2 knockdown reduces drug-resistance protein expression caused by WBP2 overexpression, placing AMOTL2 as a mediator in the ITCH/WBP2/AMOTL2/c-JUN chemoresistance axis. RNA sequencing, siRNA knockdown epistasis, immunoblotting for phospho-c-JUN, in vivo xenograft with proteasome inhibitor (MG132) Biochemical pharmacology Low 39709035
2025 AMOTL2 is identified as a direct cellular target of celastrol by activity-based protein profiling (ABPP); celastrol-AMOTL2 binding activates the Hippo pathway, promoting YAP1 phosphorylation and degradation; AMOTL2 knockdown attenuates celastrol-induced cardiomyocyte apoptosis by enhancing YAP1 expression and mitochondrial biogenesis. Activity-based protein profiling (ABPP) for direct target identification, shRNA knockdown of AMOTL2, YAP1 phosphorylation/expression assays, mitochondrial biogenesis assays, in vivo mouse cardiotoxicity model Chemico-biological interactions Medium 41412440
2025 AMOTL2 inhibits Zika virus replication by promoting the host type I interferon response; AMOTL2 modulates STAT1 levels and activation in response to type I IFN, promoting downstream expression of interferon-stimulated genes. CRISPR knockout screen for ZIKV host factors, AMOTL2 KO validation, STAT1 activation assays (phospho-STAT1, STAT1 protein levels), ISG expression assays Proceedings of the National Academy of Sciences of the United States of America Medium 40892926
2025 AmotL2 maintains junctional architecture, actomyosin tension, and appropriate cell packing in endothelial cells; loss of AmotL2 disrupts tension homeostasis, increases tissue compaction, and prevents vascular branch regression (pruning) despite normal perfusion in zebrafish; Yap1 plays an opposing stabilizing role, and AmotL2 and Yap1 together constitute a mechanosensitive balancing module for flow-guided vascular remodeling. Zebrafish live imaging, quantitative vascular topology analysis, amotL2 and yap1 mutant/knockdown genetic analysis, actomyosin tension measurements, junctional remodeling assays bioRxivpreprint Medium bio_10.1101_2025.11.19.689183

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Hypoxic Tumor-Derived Exosomal Long Noncoding RNA UCA1 Promotes Angiogenesis via miR-96-5p/AMOTL2 in Pancreatic Cancer. Molecular therapy. Nucleic acids 153 32942233
2015 Phosphorylation of the Hippo Pathway Component AMOTL2 by the mTORC2 Kinase Promotes YAP Signaling, Resulting in Enhanced Glioblastoma Growth and Invasiveness. The Journal of biological chemistry 81 25998128
2011 Angiomotin-like2 gene (amotl2) is required for migration and proliferation of endothelial cells during angiogenesis. The Journal of biological chemistry 64 21937427
2014 AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion. Nature communications 60 24806444
2014 AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion. Nature communications 53 25080976
2007 Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation. Development (Cambridge, England) 49 17293535
2012 The Amotl2 gene inhibits Wnt/β-catenin signaling and regulates embryonic development in zebrafish. The Journal of biological chemistry 47 22362771
2013 Amotl2 interacts with LL5β, localizes to podosomes and regulates postsynaptic differentiation in muscle. Journal of cell science 44 23525008
2017 The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatching. Scientific reports 26 28842668
2020 AMOTL2 inhibits JUN Thr239 dephosphorylation by binding PPP2R2A to suppress the proliferation in non-small cell lung cancer cells. Biochimica et biophysica acta. Molecular cell research 19 32950569
2023 The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms. Nature cardiovascular research 14 39195920
2024 The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway. Cell death & disease 12 38956029
2021 MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis. Scientific reports 11 33707576
2021 AmotL2, IQGAP1, and FKBP51 Scaffold Proteins in Glioblastoma Stem Cell Niches. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 11 34165350
2021 AMOTL2‑knockdown promotes the proliferation, migration and invasion of glioma by regulating β‑catenin nuclear localization. Oncology reports 10 34036399
2017 AmotL2 integrates polarity and junctional cues to modulate cell shape. Scientific reports 10 28790366
2013 AMOTL2 interaction with TAZ causes the inhibition of surfactant proteins expression in lung cells. Gene 10 23911299
2024 E3 ubiquitin ligase ITCH-mediated proteasomal degradation of WBP2 sensitizes breast cancer cells to chemotherapy through restraining AMOTL2/c-JUN axis. Biochemical pharmacology 8 39709035
2022 FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats. Cells 8 35563891
2021 AMOTL2 restrains transforming growth factor-β1-induced proliferation and extracellular matrix deposition of airway smooth muscle cells via the down-regulation of YAP1 activation. Environmental toxicology 8 34323359
2022 Myocyte enhancer factor 2D promotes hepatocellular carcinoma through AMOTL2/YAP signaling that inhibited by luteolin. International journal of clinical and experimental pathology 6 35698637
2024 LCCP exposure leads to skin cell senescence damage by triggering oxidative stress mediated by mitochondrial Ca2+ overload. International immunopharmacology 5 39467346
2024 Changes in AmotL2 Expression in Cells of the Human Enteral Nervous System in Oxaliplatin-Induced Enteric Neuropathy. Biomedicines 4 39335466
2021 AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation. Life science alliance 4 34404733
2023 Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2. eLife 3 38126343
2025 Bone marrow mesenchymal stem cells senescence induced by LCCP through activation of cGAS-STING-mediated inflammation. Ecotoxicology and environmental safety 2 40154222
2023 Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion. Cells 2 37443716
2025 Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus. Proceedings of the National Academy of Sciences of the United States of America 1 40892926
2025 Celastrol induces cardiotoxicity by directly targeting AMOTL2 and inhibiting YAP1/PGC-1α/TFAM-dependent mitochondrial biogenesis. Chemico-biological interactions 1 41412440
2025 Circ_0001461 Regulates Colorectal Cancer Growth, Movement and Immune Escape Through miR-532-3p/AMOTL2. Biochemical genetics 0 40569478
2023 Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2. bioRxiv : the preprint server for biology 0 37131806

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