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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Perera, G. K. Sachith Dbouk, Hashem A. Cobb, Melanie H. Brekken, Rolf A. Weil, Lauren M. Dellinger, Michael T. Pearson, Gray |
| Description | Author Affiliation: Dbouk HA ( Departments of Pharmacology and.); Weil LM ( Departments of Pharmacology and.); Perera GK ( Departments of Pharmacology and.); Dellinger MT ( Surgery.); Pearson G ( Departments of Pharmacology and Simmons Comprehensive Cancer Center, and.); Brekken RA ( Departments of Pharmacology and Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390.); Cobb MH ( Departments of Pharmacology and melanie.cobb@utsouthwestern.edu.); |
| Abstract | The with no lysine (K) (WNK) family of enzymes is best known for control of blood pressure through regulation of the function and membrane localization of ion cotransporters. In mice, global as well as endothelial-specific WNK1 gene disruption results in embryonic lethality due to angiogenic and cardiovascular defects. WNK1(-/-) embryos can be rescued by endothelial-specific expression of a constitutively active form of the WNK1 substrate protein kinase OSR1 (oxidative stress responsive 1). Using human umbilical vein endothelial cells (HUVECs), we explored mechanisms underlying the requirement of WNK1-OSR1 signaling for vascular development. WNK1 is required for cord formation in HUVECs, but the actions of the two major WNK1 effectors, OSR1 and its close relative SPAK (STE20/SPS1-related proline-, alanine-rich kinase), are distinct. SPAK is important for endothelial cell proliferation, whereas OSR1 is required for HUVEC chemotaxis and invasion. We also identified the zinc-finger transcription factor Slug in WNK1-mediated control of endothelial functions. Our study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells and an unanticipated link between WNK1 and Slug that is important for angiogenesis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 45 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Human Umbilical Vein Endothelial Cells Metabolism Intracellular Signaling Peptides And Proteins Protein-Serine-Threonine Kinases Animals Cell Proliferation Physiology Gene Expression Regulation Cytology Genetics Mice Mice, Knockout Minor Histocompatibility Antigens Neovascularization, Physiologic Signal Transduction Transcription Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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