ArticleProceedings of the National Academy of Sciences of the United States of America2018
Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 129 citations in OpenAlex.
- A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.Investigative ophthalmology & visual science · 2020Trial
- Cell-Specific Roles of Angiopoietin-2 in CKD.Journal of the American Society of Nephrology : JASN · 2026Article
- Article
- Altered Vascular and Angiogenic Transcripts in the Neurogenic Niche in Neuroinflammatory-Type Schizophrenia.Schizophrenia bulletin · 2026Article
- Review
- A high-sensitivity TIE2-GRB2 BRET platform for functional and pharmacologic profiling of pathogenic variants associated with venous malformations.Angiogenesis · 2026Article
- Article
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- Disrupting VE-cadherin Y685 phosphorylation inhibits development of experimental diabetic and prediabetic retinopathy.The Journal of clinical investigation · 2026Article
- Review
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage.JCI insight · 2026Article
- Development of striated muscle microvasculature across the perinatal period in lambs.The Journal of physiology · 2026Article
- TIE2-positive cells in the nucleus pulposus with a purpose: the who, what and why.Journal of biomedical science · 2026Review
- A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.Translational vision science & technology · 2026Article
- The role of the vascular niche in regulating kidney tubulointerstitial fibrosis.Kidney international · 2026Review
- Pericytes as key mediators of microenvironmental signaling crosstalk: implications in vascular diseases and cancer.Frontiers in cell and developmental biology · 2026Review
- Single nucleus RNA sequencing unveils relationship between microglia and endothelial cells in mixed Alzheimer's disease and vascular pathology.Neurobiology of disease · 2025Article
- Organ-specific features of human kidney lymphatics are disrupted in chronic transplant rejection.The Journal of clinical investigation · 2025Article
- Pretreatment serum angiopoietin-2 predicts prognosis and liver functional reserve after successful HCV eradication with sofosbuvir and velpatasvir in patients with HCV-related decompensated cirrhosis.Journal of gastroenterology · 2025Article
- Angiopoietin-2 binds to FGFR2, inhibits FGF-FGFR2 signaling, and delays cutaneous wound healing by inhibiting wound angiogenesis.Angiogenesis · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated inhibition of TIE2 in blood vessels is linked to vascular leak, inflammation, and metastasis. Using conditional knockout studies in mice, we show TIE2 is predominantly activated by ANGPT1 in the cardiovascular system and by ANGPT2 in the lymphatic vasculature. Mechanisms underlying opposing actions of ANGPT2 in blood vs. lymphatic endothelium are poorly understood. Here we show the endothelial-specific phosphatase VEPTP (vascular endothelial protein tyrosine phosphatase) determines TIE2 response to ANGPT2. VEPTP is absent from lymphatic endothelium in mouse in vivo, permitting ANGPT2/TIE2-mediated lymphangiogenesis. Inhibition of VEPTP converts ANGPT2 into a potent TIE2 activator in blood endothelium. Our data support a model whereby VEPTP functions as a rheostat to modulate ANGPT2 ligand effect on TIE2.
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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.