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Citations to this article

Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure
Masaaki Hayashi, … , Richard J. Ulevitch, Jiing-Dwan Lee
Masaaki Hayashi, … , Richard J. Ulevitch, Jiing-Dwan Lee
Published April 15, 2004
Citation Information: J Clin Invest. 2004;113(8):1138-1148. https://doi.org/10.1172/JCI19890.
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Article Vascular biology Article has an altmetric score of 3

Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure

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Abstract

Big mitogen-activated protein kinase 1 (BMK1), also known as ERK5, is a member of the MAPK family. Genetic ablation of BMK1 in mice leads to embryonic lethality, precluding the exploration of pathophysiological roles of BMK1 in adult mice. We generated a BMK1 conditional mutation in mice in which disruption of the BMK1 gene is under the control of the inducible Mx1-Cre transgene. Ablation of BMK1 in adult mice led to lethality within 2–4 weeks after the induction of Cre recombinase. Physiological analysis showed that the blood vessels became abnormally leaky after deletion of the BMK1 gene. Histological analysis revealed that, after BMK1 ablation, hemorrhages occurred in multiple organs in which endothelial cells lining the blood vessels became round, irregularly aligned, and, eventually, apoptotic. In vitro removal of BMK1 protein also led to the death of endothelial cells partially due to the deregulation of transcriptional factor MEF2C, which is a direct substrate of BMK1. Additionally, endothelial-specific BMK1-KO leads to cardiovascular defects identical to that of global BMK1-KO mutants, whereas, surprisingly, mice lacking BMK1 in cardiomyocytes developed to term without any apparent defects. Taken together, the data provide direct genetic evidence that the BMK1 pathway is critical for endothelial function and for maintaining blood vessel integrity.

Authors

Masaaki Hayashi, Sung-Woo Kim, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, E. Dale Abel, Brian Eliceiri, Young Yang, Richard J. Ulevitch, Jiing-Dwan Lee

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 1 4 7 4 3 6 3 2 11 8 10 9 7 6 3 8 6 9 5 7 7 2 128
Citation information
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Citations to this article in year 2013 (7)

Title and authors Publication Year
Endothelial FoxO1 is an intrinsic regulator of thrombospondin 1 expression that restrains angiogenesis in ischemic muscle
E Roudier, M Milkiewicz, O Birot, D Slopack, A Montelius, T Gustafsson, JH Paik, RA DePinho, GP Casale, II Pipinos, TL Haas
Angiogenesis 2013
X-ray Crystal Structure of ERK5 (MAPK7) in Complex with a Specific Inhibitor
JM Elkins, J Wang, X Deng, MJ Pattison, JS Arthur, T Erazo, N Gomez, JM Lizcano, NS Gray, S Knapp
Journal of Medicinal Chemistry 2013
Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: New insights from ERK5 MAP kinase
YW Pan, DR Storm, Z Xia
Neurobiology of Learning and Memory 2013
The wooly mutation (wly) on mouse chromosome 11 is associated with a genetic defect in Fam83g
LA Radden, KM Child, EB Adkins, DV Spacek, AM Feliciano, TR King
BMC Research Notes 2013
Extracellular Signal-Regulated Kinase 5: A Potential Therapeutic Target for Malignant Mesotheliomas
A Shukla, JM Miller, C Cason, M Sayan, MB MacPherson, SL Beuschel, J Hillegass, PM Vacek, HI Pass, BT Mossman
Clinical cancer research 2013
Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) Module
G Glatz, G Gogl, A Alexa, A Remenyi
The Journal of biological chemistry 2013
ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma.
Arias-González L, Moreno-Gimeno I, del Campo AR, Serrano-Oviedo L, Valero ML, Esparís-Ogando A, de la Cruz-Morcillo MÁ, Melgar-Rojas P, García-Cano J, Cimas FJ, Hidalgo MJ, Prado A, Callejas-Valera JL, Nam-Cha SH, Giménez-Bachs JM, Salinas-Sánchez AS, Pandiella A, del Peso L, Sánchez-Prieto R
Neoplasia (New York, N.Y.) 2013

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