Serum/glucocorticoid-regulated kinase 1 as a novel transcriptional target of bone morphogenetic protein-ALK1 receptor signaling in vascular endothelial cells

Angiogenesis
Mutsumi ArakiOsamu Nakagawa

Abstract

Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis. Mutations in ALK1/ACVRL1 and other signal-related genes are implicated in human vascular diseases, and the Alk1/Acvrl1 deletion in mice causes severe impairment of vascular formation and embryonic lethality. In the microarray screen to search for novel downstream genes of ALK1 signaling, we found that the mRNA and protein expression of serum/glucocorticoid-regulated kinase 1 (SGK1) was rapidly up-regulated by the BMP9 stimulation of cultured human endothelial cells. The increase in SGK1 mRNA was completely blocked by the transcriptional inhibitor actinomycin D and significantly suppressed by the siRNA treatment against the co-SMAD transcription factor SMAD4. Upon the BMP9 treatment of endothelial cells, phosphorylated SMAD1/5/9 bound to a consensus site upstream of the SGK1 gene, which was necessary for BMP9-dependent increment of the luciferase reporter activity driven by the SGK1 proximal enhancer. The Sgk1 mRNA expression in mouse embryos was enriched in vascular endothelial cells at embryonic day 9.0-9.5, at which Sgk1 null mice showed embryonic lethality due to abnormal vascular formati...Continue Reading

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Citations

Aug 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Aleksandra LaweraWei Li
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Ting XinFang Hu
Oct 30, 2019·Journal of Receptor and Signal Transduction Research·Xinyu Song, Tianchang Li
Oct 16, 2019·Journal of Cellular Physiology·Dezhi Huang, Yugang Jiang
Jun 4, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yukihiro HaradaOsamu Nakagawa
Jul 20, 2021·Journal of Cellular Physiology·Jun ZhangZhi-Ren Zhang

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Datasets Mentioned

BETA
GSE27661

Methods Mentioned

BETA
immunoprecipitation
ChIP

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