ArticleMolecular and cellular biology2016
Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical for Lymphatic Vascular Development and Function.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- Modulation of calcium signaling and metabolic pathways in endothelial cells with magnetic fields.Nanoscale advances · 2024Article
- Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.Science advances · 2023Article
- Article
- Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways.International journal of molecular sciences · 2022Article
- The molecular basis of the dichotomous functionality of MAP4K4 in proliferation and cell motility control in cancer.Frontiers in oncology · 2022Review
- MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.Oncogene · 2021Article
- A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development.BMB reports · 2021Review
- Role of RASA1 in cancer: A review and update (Review).Oncology reports · 2020Review
- The Misshapen subfamily of Ste20 kinases regulate proliferation in the aging mammalian intestinal epithelium.Journal of cellular physiology · 2019Article
- Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.Neuron · 2019Article
- Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity.American journal of physiology. Endocrinology and metabolism · 2017Article
- Vascular heterogeneity and specialization in development and disease.Nature reviews. Molecular cell biology · 2017Review
- Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.Trends in endocrinology and metabolism: TEM · 2016Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities, and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression. Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate.
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Registered trials
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