ArticlePloS one2014
Zebrafish WNK lysine deficient protein kinase 1 (wnk1) affects angiogenesis associated with VEGF signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation.Scientific reports · 2024Article
- Bioinformatics analysis identifies WNK1 gene as a potential biomarker for cholangiocarcinoma diagnosis and immune infiltration.Journal, genetic engineering & biotechnology · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Unanticipated domain requirements for Drosophila Wnk kinase in vivo.PLoS genetics · 2023Article
- Review
- A metazoan-specific C-terminal motif in EXC-4 and Gα-Rho/Rac signaling regulate cell outgrowth during tubulogenesis in C. elegans.Development (Cambridge, England) · 2022Article
- WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy.International journal of molecular sciences · 2022Article
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- Angiogenesis in gastrointestinal stromal tumors: From bench to bedside.World journal of gastrointestinal oncology · 2022Review
- WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- Loss of WNK1 Suppressed the Malignant Behaviors of Hepatocellular Carcinoma Cells by Promoting Autophagy and Activating AMPK Pathway.Disease markers · 2022Article
- With no lysine kinases: the key regulatory networks and phytohormone cross talk in plant growth, development and stress response.Plant cell reports · 2021Review
- Upstream Open Reading Frame Mediated Translation of WNK8 Is Required for ABA Response inInternational journal of molecular sciences · 2021Article
- WNK1 Enhances Migration and Invasion in Breast Cancer Models.Molecular cancer therapeutics · 2021Article
- Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease.Journal of clinical medicine · 2020Article
- Article
- WNK1-OSR1/SPAK KINASE CASCADE IS IMPORTANT FOR ANGIOGENESIS.Transactions of the American Clinical and Climatological Association · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The WNK1 (WNK lysine deficient protein kinase 1) protein is a serine/threonine protein kinase with emerging roles in cancer. WNK1 causes hypertension and hyperkalemia when overexpressed and cardiovascular defects when ablated in mice. In this study, the role of Wnk1 in angiogenesis was explored using the zebrafish model. There are two zebrafish wnk1 isoforms, wnk1a and wnk1b, and both contain all the functional domains found in the human WNK1 protein. Both isoforms are expressed in the embryo at the initiation of angiogenesis and in the posterior cardinal vein (PCV), similar to fms-related tyrosine kinase 4 (flt4). Using morpholino antisense oligonucleotides against wnk1a and wnk1b, we observed that wnk1 morphants have defects in angiogenesis in the head and trunk, similar to flk1/vegfr2 morphants. Furthermore, both wnk1a and wnk1b mRNA can partially rescue the defects in vascular formation caused by flk1/vegfr2 knockdown. Mutation of the kinase domain or the Akt/PI3K phosphorylation site within wnk1 destroys this rescue capability. The rescue experiments provide evidence that wnk1 is a downstream target for Vegfr2 (vascular endothelial growth factor receptor-2) and Akt/PI3K signaling and thereby affects angiogenesis in zebrafish embryos. Furthermore, we found that knockdown of vascular endothelial growth factor receptor-2 (flk1/vegfr2) or vascular endothelial growth factor receptor-3 (flt4/vegfr3) results in a decrease in wnk1a expression, as assessed by in situ hybridization and q-RT-PCR analysis. Thus, the Vegf/Vegfr signaling pathway controls angiogenesis in zebrafish via Akt kinase-mediated phosphorylation and activation of Wnk1 as well as transcriptional regulation of wnk1 expression.
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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.