ArticleNature2015
MAP4K4 regulates integrin-FERM binding to control endothelial cell motility.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 153 citations in OpenAlex.
- Moesin is an αCellular and molecular life sciences : CMLS · 2026Article
- Pathogenic mechanism of extracranial arteriovenous malformations: insights from clinical, pathological, and genetic analyses.Virchows Archiv : an international journal of pathology · 2026Article
- Alpha 5 integrin as a prognostic biomarker for survival in carcinomas: a systematic review.Discover oncology · 2025Review
- In silico screening and in vitro biological evaluation reveal Queuine as a promising MAP4K4 inhibitor for treating pancreatic cancer.BMC biotechnology · 2025Article
- Modulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade.Cell reports. Medicine · 2025Article
- MAP4K4 aggravates microvascular anomalies in diabetic retinopathy in a YTHDF2-dependent manner.Diabetologia · 2025Article
- Machine learning-based prediction reveals kinase MAP4K4 regulates neutrophil differentiation through phosphorylating apoptosis-related proteins.PLoS computational biology · 2025Article
- The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.Frontiers of medicine · 2024Article
- SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation.Open biology · 2024Article
- Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB.NPJ Regenerative medicine · 2024Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
- The Effect of Parent Cell Type on Small Extracellular Vesicle-Derived Vehicle Functionality.Advanced biology · 2024Article
- Review
- RAGE plays key role in diabetic retinopathy: a review.Biomedical engineering online · 2023Review
- Myeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB.Nature communications · 2023Article
- In silico identification and biological evaluation of a selective MAP4K4 inhibitor against pancreatic cancer.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- MAP4K4 regulates forces at cell-cell and cell-matrix adhesions to promote collective cell migration.Life science alliance · 2023Article
- MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.Oncogene · 2023Article
- Review
- Phosphorylation of NF2 at Serine-13 by MAP4K family kinases mediates pathological angiogenesis.Protein & cell · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell migration is a stepwise process that coordinates multiple molecular machineries. Using in vitro angiogenesis screens with short interfering RNA and chemical inhibitors, we define here a MAP4K4-moesin-talin-β1-integrin molecular pathway that promotes efficient plasma membrane retraction during endothelial cell migration. Loss of MAP4K4 decreased membrane dynamics, slowed endothelial cell migration, and impaired angiogenesis in vitro and in vivo. In migrating endothelial cells, MAP4K4 phosphorylates moesin in retracting membranes at sites of focal adhesion disassembly. Epistasis analyses indicated that moesin functions downstream of MAP4K4 to inactivate integrin by competing with talin for binding to β1-integrin intracellular domain. Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells. Additionally, α5β1-integrin blockade reversed the membrane retraction defects associated with loss of Map4k4 in vitro and in vivo. Our study uncovers a novel aspect of endothelial cell migration. Finally, loss of MAP4K4 function suppressed pathological angiogenesis in disease models, identifying MAP4K4 as a potential therapeutic target.
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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.