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      Gαq/p63RhoGEF interaction in RhoA/Rho kinase signaling: investigation in Gitelman's syndrome and implications with hypertension.

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          Abstract

          Gitelman's syndrome (GS) presents normo-hypotension and absence of cardiovascular-renal remodeling despite high angiotensin II (Ang II), activation of renin-angiotensin-aldosterone system and is a human model of endogenous antagonism of Ang II signaling, opposite to hypertension. GS's clinical presentation leads to questions regarding what features might be responsible. One area of investigation involves Ang II signaling. In hypertensive patients, RhoA/Rho kinase (RhoA/ROCK) pathway activation by Ang II is involved in hypertension development/maintenance and induction of long-term consequences (cardiovascular-renal remodeling), while GS has reduced p63RhoGEF gene and protein levels and ROCK activity. Ang II signaling is mediated by Gαq, which interacts with p63RhoGEF via the α6-αN linker connecting p63RhoGEF's DH and PH domains acting as a conformational switch to activate RhoA/ROCK signaling.

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          Author and article information

          Journal
          J Endocrinol Invest
          Journal of endocrinological investigation
          Springer Science and Business Media LLC
          1720-8386
          0391-4097
          Mar 2018
          : 41
          : 3
          Affiliations
          [1 ] Department of Medicine (DIMED), Nephrology, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy.
          [2 ] Hypertension, University of Padova, Padua, Italy.
          [3 ] Department of Nutrition, University of California, Davis, USA.
          [4 ] Department of Medicine (DIMED), Nephrology, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy. renzcalo@unipd.it.
          Article
          10.1007/s40618-017-0749-0
          10.1007/s40618-017-0749-0
          28840514
          65a34403-8382-4975-8a4a-362d830ad44f
          History

          Cardiovascular remodeling,Gitelman’s syndrome,Hypertension,RhoA/Rho kinase signaling,p63RhoGEF

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