ArticleMolecular and cellular biology2015
p21-Activated Kinase 2 Regulates Endothelial Development and Function through the Bmk1/Erk5 Pathway.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Targeting P21-Activated Kinase 2 as a Novel Therapeutic Approach to Mitigate Endoplasmic Reticulum Stress in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2025Article
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis.Journal of the American Heart Association · 2024Article
- Inhibition of P21-activated kinases 1 and 4 synergistically suppresses the growth of pancreatic cancer by stimulating anti-tumour immunity.Cell communication and signaling : CCS · 2024Article
- PAK2 is necessary for myelination in the peripheral nervous system.Brain : a journal of neurology · 2024Article
- A novel pipeline for prioritizing cancer type-specific therapeutic vulnerabilities using DepMap identifies PAK2 as a target in head and neck squamous cell carcinomas.Molecular oncology · 2024Article
- Review
- PAK2 is essential for chromosome alignment in metaphase I oocytes.Cell death & disease · 2023Article
- Loss-of-Function of p21-Activated Kinase 2 Links BMP Signaling to Neural Tube Patterning Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022Article
- Review
- Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2022Article
- ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.Cancers · 2022Article
- Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Tumors by Restricting Downstream Hedgehog and Wnt Signaling.Molecular cancer research : MCR · 2022Article
- Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy.iScience · 2022Article
- p21-Activated kinases as promising therapeutic targets in hematological malignancies.Leukemia · 2022Review
- Pak2 Regulation of Nrf2 Serves as a Novel Signaling Nexus Linking ER Stress Response and Oxidative Stress in the Heart.Frontiers in cardiovascular medicine · 2022Article
- Pak2 reduction induces a failure of early embryonic development in mice.Reproductive biology and endocrinology : RB&E · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
p21-activated kinases (Paks) have been shown to regulate cytoskeleton rearrangements, cell proliferation, attachment, and migration in a variety of cellular contexts, including endothelial cells. However, the role of endothelial Pak in embryo development has not been reported, and currently, there is no consensus on the endothelial function of individual Pak isoforms, in particular p21-activated kinase 2 (Pak2), the main Pak isoform expressed in endothelial cells. In this work, we employ genetic and molecular studies that show that Pak2, but not Pak1, is a critical mediator of development and maintenance of endothelial cell function. Endothelial depletion of Pak2 leads to early embryo lethality due to flawed blood vessel formation in the embryo body and yolk sac. In adult endothelial cells, Pak2 depletion leads to severe apoptosis and acute angiogenesis defects, and in adult mice, endothelial Pak2 deletion leads to increased vascular permeability. Furthermore, ubiquitous Pak2 deletion is lethal in adult mice. We show that many of these defects are mediated through a newly unveiled Pak2/Bmk1 pathway. Our results demonstrate that endothelial Pak2 is essential during embryogenesis and also for adult blood vessel maintenance, and they also pinpoint the Bmk1/Erk5 pathway as a critical mediator of endothelial Pak2 signaling.
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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.