ArticleHuman molecular genetics2015
Common and specific effects of TIE2 mutations causing venous malformations.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 109 citations in OpenAlex.
- Review
- A high-sensitivity TIE2-GRB2 BRET platform for functional and pharmacologic profiling of pathogenic variants associated with venous malformations.Angiogenesis · 2026Article
- Multifocal Sporadic Venous Malformations in a Child Caused by a Novel Somatic Double Mutation of the TEK Gene: A Case Report and Literature Review.Molecular genetics & genomic medicine · 2026Review
- Constitutive, Mosaic Expression of TIE2 p.L914F During Mouse Development Causes Venous Malformation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Polymeric rapamycin nanoparticles encapsulating ponatinib cause regression of venous malformations in mice.Science translational medicine · 2026Article
- A human endothelial and adipose stem cell-based co-culture model for venous malformations.Angiogenesis · 2026Article
- Constitutive, mosaic expression of TIE2 p.L914F during mouse development causes formation of venous malformation.bioRxiv : the preprint server for biology · 2026Article
- Identification of pathological CD133+ endothelial cells in venous malformations.Frontiers in cardiovascular medicine · 2026Article
- Advances in genetics, signaling, and modeling of venous malformations.Frontiers in cardiovascular medicine · 2026Review
- Increased metallopeptidase activity, compromised endothelial integrity and impaired pathogen recognition revealed by transcriptomics inCurrent research in parasitology & vector-borne diseases · 2026Article
- Semaphorin 3A and 3F Promote Lumen Expansion in TIE2-Mutated Venous Malformation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Lack of association betweenBiochemistry and biophysics reports · 2025Article
- TIE1-dependent lymphatic vascular remodeling is mediated by its second tyrosine kinase domain.Development (Cambridge, England) · 2025Article
- Genetic mutation and blue rubber bleb nevus syndrome: case reports and literature review.Frontiers in genetics · 2025Article
- Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development.International journal of biological sciences · 2025Review
- VE-PTP controls a fluid shear stress set point that governs cell morphological responses through Tie-2.Frontiers in cell and developmental biology · 2025Article
- Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2Angiogenesis · 2024Article
- The Role of Medical Management in Vascular Anomalies.Seminars in interventional radiology · 2024Review
- NRASPediatric blood & cancer · 2024Article
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Venous malformations (VMs) are localized defects in vascular morphogenesis frequently caused by mutations in the gene for the endothelial tyrosine kinase receptor TIE2. Here, we report the analysis of a comprehensive collection of 22 TIE2 mutations identified in patients with VM, either as single amino acid substitutions or as double-mutations on the same allele. Using endothelial cell (EC) cultures, mouse models and ultrastructural analysis of tissue biopsies from patients, we demonstrate common as well as mutation-specific cellular and molecular features, on the basis of which mutations cluster into categories that correlate with data from genetic studies. Comparisons of double-mutants with their constituent single-mutant forms identified the pathogenic contributions of individual changes, and their compound effects. We find that defective receptor trafficking and subcellular localization of different TIE2 mutant forms occur via a variety of mechanisms, resulting in attenuated response to ligand. We also demonstrate, for the first time, that TIE2 mutations cause chronic activation of the MAPK pathway resulting in loss of normal EC monolayer due to extracellular matrix (ECM) fibronectin deficiency and leading to upregulation of plasminogen/plasmin proteolytic pathway. Corresponding EC and ECM irregularities are observed in affected tissues from mouse models and patients. Importantly, an imbalance between plasminogen activators versus inhibitors would also account for high d-dimer levels, a major feature of unknown cause that distinguishes VMs from other vascular anomalies.
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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.