ArticleJCI insight2023
Release of STK24/25 suppression on MEKK3 signaling in endothelial cells confers cerebral cavernous malformation.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- Human stem cell models in cerebral cavernous malformations.Stem cell research & therapy · 2026Review
- Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice.Disease models & mechanisms · 2026Article
- MEKK3 bridges gut-brain communication and cerebral cavernous malformation pathogenesis.Cell death discovery · 2026Review
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- Article
- TLNRD1-CCM2 interaction maintains endothelial actin networks through a KLF2/4-independent mechanism.JVS-vascular science · 2026Article
- STK25 Loss Augments Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Stability in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LncRNA OIP5-AS1 promotes immune evasion in abdominal aortic aneurysm cells by recruiting MDSCs and inhibiting CD8 + T cells through STK24 upregulation.Cytotechnology · 2025Article
- TLNRD1 is a CCM complex component and regulates endothelial barrier integrity.The Journal of cell biology · 2024Article
- Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in cerebral cavernous malformation (CCM) genes and gain-of-function mutation in the MAP3K3 gene encoding MEKK3 cause CCM. Deficiency of CCM proteins leads to the activation of MEKK3-KLF2/4 signaling, but it is not clear how this occurs. Here, we demonstrate that deletion of the CCM3 interacting kinases STK24/25 in endothelial cells causes defects in vascular patterning during development as well as CCM lesion formation during postnatal life. While permanent deletion of STK24/25 in endothelial cells caused developmental defects of the vascular system, inducible postnatal deletion of STK24/25 impaired angiogenesis in the retina and brain. More importantly, deletion of STK24/25 in neonatal mice led to the development of severe CCM lesions. At the molecular level, a hybrid protein consisting of the STK kinase domain and the MEKK3 interacting domain of CCM2 rescued the vascular phenotype caused by the loss of ccm gene function in zebrafish. Our study suggests that CCM2/3 proteins act as adapters to allow recruitment of STK24/25 to limit the constitutive MEKK3 activity, thus contributing to vessel stability. Loss of STK24/25 causes MEKK3 activation, leading to CCM lesion formation.
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