The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure.

Nature Medicine
Christophe GuilluyGervaise Loirand

Abstract

Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, how RhoA is activated and whether it has a causative role in hypertension remains unclear. Here we provide evidence that Arhgef1 is the RhoA guanine exchange factor specifically responsible for angiotensin II-induced activation of RhoA signaling in arterial smooth muscle cells. We found that angiotensin II activates Arhgef1 through a previously undescribed mechanism in which Jak2 phosphorylates Tyr738 of Arhgef1. Arhgef1 inactivation in smooth muscle induced resistance to angiotensin II-dependent hypertension in mice, but did not affect normal blood pressure regulation. Our results show that control of RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension.

References

Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·L HeinV J Dzau
Jun 26, 1998·Science·T KozasaP C Sternweis
Feb 20, 1999·The Journal of Biological Chemistry·S FukuharaJ S Gutkind
Dec 22, 1999·The Journal of Biological Chemistry·J FengT Nakano
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·P ParadisM Nemer
Mar 22, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y Y LiuM C Cabot
Apr 9, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y MukaiA Takeshita
Nov 8, 2001·The Journal of Biological Chemistry·Clark D WellsPaul C Sternweis
Sep 10, 2002·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·R M Touyz, C Berry
Nov 2, 2002·Hypertension·Janelle R KeysAndrea D Eckhart
Jan 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nobuchika SuzukiTohru Kozasa
May 16, 2003·Lancet·Jan A StaessenWillem H Birkenhäger
Feb 27, 2004·Cardiovascular Research·Allan D Struthers, Thomas M MacDonald
May 7, 2004·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Nobuyuki MorikiTakeshi Nakano
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Kent L RossmanJohn Sondek
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Aron B Jaffe, Alan Hall
Jan 25, 2006·Hypertension·Ernesto L Schiffrin
Feb 14, 2006·Methods in Enzymology·Rafael García-MataKeith Burridge
Feb 18, 2006·Circulation Research·Gervaise LoirandPierre Pacaud
Jul 28, 2006·American Journal of Physiology. Cell Physiology·Puja K Mehta, Kathy K Griendling
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Steven D CrowleyThomas M Coffman
Nov 28, 2006·Trends in Cell Biology·Rafael García-Mata, Keith Burridge
May 29, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Amy K L Banes-BerceliMario B Marrero
Jun 2, 2007·Cell·Johannes L BosAlfred Wittinghofer
Mar 28, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Catherine A LemariéErnesto L Schiffrin

❮ Previous
Next ❯

Citations

Jan 6, 2011·Current Hypertension Reports·Shigeru Shibata, Toshiro Fujita
Jan 29, 2011·Current Hypertension Reports·Aurelie Nguyen Dinh Cat, Rhian M Touyz
Apr 1, 2011·Expert Reviews in Molecular Medicine·Carmine SavoiaRhian M Touyz
Feb 6, 2010·Nature Medicine·Kenneth E Bernstein, Sebastien Fuchs
Apr 3, 2012·Cardiovascular Research·Patrick LacolleyJean-Baptiste Michel
May 29, 2012·Cardiovascular Research·Gilles KauffensteinDaniel Henrion
Aug 30, 2011·Journal of Biochemistry·Tohru KozasaNobuchika Suzuki
Nov 16, 2010·Current Opinion in Nephrology and Hypertension·Johannes Stegbauer, Thomas M Coffman
Apr 5, 2013·Clinical and Experimental Pharmacology & Physiology·Duncan J Campbell
Aug 5, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Amy K L Banes-BerceliMichael W Brands
Aug 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Matt D MedlinChristopher P Mack
Jun 17, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Christopher P Mack
Oct 16, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Lihong ChenYoufei Guan
Jul 13, 2011·The Journal of Clinical Investigation·Sunny Yang XiangJoan Heller Brown
Jan 28, 2014·PloS One·Swapnil S KherRebecca A Worthylake
Oct 8, 2011·Journal of the American Society of Nephrology : JASN·Anna Greka, Peter Mundel
Sep 21, 2011·Future Cardiology·Michelle SurmaJianjian Shi
Apr 25, 2014·Current Hypertension Reports·Augusto C MontezanoRhian M Touyz
Jul 20, 2011·Nature Chemical Biology·Jacqueline Cherfils, Mahel Zeghouf
Apr 23, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Wen SuMing C Gong
Dec 25, 2012·Experimental Cell Research·Jakob Nikolas Kather, Jens Kroll
Aug 21, 2012·Trends in Cardiovascular Medicine·Ko Momotani, Avril V Somlyo
Apr 10, 2012·The Canadian Journal of Cardiology·Daian Chen, Thomas M Coffman
Aug 13, 2011·Journal of Molecular Graphics & Modelling·Kh Dhanachandra SinghSelvaraman Nagamani
Dec 5, 2015·Frontiers in Pharmacology·Svenja HartmannSusanne Lutz
Oct 1, 2015·Journal of the American Society of Hypertension : JASH·Songcang ChenDevendra K Agrawal
Nov 19, 2013·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Sebastian AlbinssonPer Hellstrand
Mar 13, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michaela GranzowJonel Trebicka
Dec 17, 2014·Small GTPases·Gervaise Loirand, Pierre Pacaud
May 20, 2015·European Journal of Pharmacology·Anukriti SinghBushra Ateeq
Jun 14, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Till F Althoff, Stefan Offermanns
Mar 12, 2015·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Verdiana RavarottoLorenzo A Calò
Nov 26, 2013·Biochimica Et Biophysica Acta·Sabrina CavinDario Diviani

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.