Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement

The Journal of Biological Chemistry
Michael HolinstatAsrar B Malik

Abstract

Heterotrimeric G-proteins of the Galpha12/13 family activate Rho GTPase through the guanine nucleotide exchange factor p115RhoGEF. Because Rho activation is also dependent on protein kinase Calpha (PKCalpha), we addressed the possibility that PKCalpha can also induce Rho activation secondary to the phosphorylation of p115RhoGEF. Studies were made using human umbilical vein endothelial cells in which we addressed the mechanisms of PKCalpha-induced Rho activation and its consequences on actin cytoskeletal changes. We observed that PKCalpha associated with p115RhoGEF within 1 min of thrombin stimulation and p115RhoGEF phosphorylation was dependent on PKCalpha. Inhibition of PKCalpha-dependent p115RhoGEF phosphorylation prevented the thrombin-induced Rho activation, indicating that the response occurred downstream of PKCalpha phosphorylation of p115RhoGEF. The regulator of G-protein signaling domain of p115RhoGEF, a GTPase activating protein for G12/13, also prevented thrombin-induced Rho activation, indicating the parallel requirement of G12/13 in signaling Rho activation via p115RhoGEF. These data demonstrate a pathway of Rho activation involving PKCalpha-dependent phosphorylation of p115RhoGEF. Thus, Rho activation in endothelia...Continue Reading

References

Sep 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C TiruppathiI Giaever
Oct 11, 1996·The Journal of Biological Chemistry·M J HartG Bollag
Feb 7, 1998·Science·A Hall
Jun 26, 1998·Science·T KozasaP C Sternweis
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·S R Coughlin
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·V P SahJ H Brown
Aug 19, 2000·Circulation Research·G P van Nieuw AmerongenV W van Hinsbergh
Oct 6, 2000·Methods : a Companion to Methods in Enzymology·R Seethala
Oct 19, 2000·Methods in Enzymology·M J HartG Bollag
Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·R SandovalC Tiruppathi
Mar 7, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·G P van Nieuw Amerongen, V W van Hinsbergh
Aug 29, 2001·Nature Structural Biology·Z ChenS R Sprang
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Oct 23, 2001·Methods in Enzymology·Clark WellsPaul C Sternweis
Nov 8, 2001·The Journal of Biological Chemistry·Clark D WellsPaul C Sternweis
Nov 24, 2001·Trends in Cell Biology·A J Ridley
Jan 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nobuchika SuzukiTohru Kozasa

❮ Previous
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Citations

Dec 6, 2005·Pflügers Archiv : European journal of physiology·Todd M Rossignol, S V Penelope Jones
Jul 1, 2009·Expert Reviews in Molecular Medicine·Puneet KumarSarah Y Yuan
Sep 9, 2005·Molecular Biology of the Cell·Jae-Ung HwangZhenbiao Yang
Jun 18, 2010·Molecular Biology of the Cell·Lisa M GodselKathleen J Green
Aug 30, 2011·Journal of Biochemistry·Tohru KozasaNobuchika Suzuki
Aug 20, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jingyan HanTatyana Voyno-Yasenetskaya
Apr 20, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brad A BryanPatricia A D'Amore
Jul 20, 2007·Molecular and Cellular Biology·Nebojsa KnezevicDolly Mehta
Sep 27, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Claudie HecquetErvin G Erdös
May 19, 2005·Arthritis Research & Therapy·Shingo NakayamadaYoshiya Tanaka
Mar 5, 2014·The Journal of Experimental Medicine·Haixia GongAsrar B Malik
Mar 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ronit Sharon-Friling, Thomas Shenk
Feb 13, 2010·Annual Review of Physiology·Yulia Komarova, Asrar B Malik
Aug 15, 2009·Cellular and Molecular Life Sciences : CMLS·Essi MyrskyKatri Lindfors
May 11, 2011·The Journal of Cell Biology·Yapeng GuJody Rosenblatt
Feb 20, 2009·British Journal of Pharmacology·Sandra Siehler
Mar 6, 2008·Journal of Cellular Biochemistry·Bruno H MeyerSandra Siehler
Dec 9, 2004·Immunology Letters·Alison M Michie, Rinako Nakagawa
Aug 8, 2006·Biochemical and Biophysical Research Communications·Sharad S SinghalSanjay Awasthi
Jul 3, 2013·Cellular Signalling·Christina R ChowTohru Kozasa
Jan 1, 2013·Cell Adhesion & Migration·Jaap D van BuulStephan Huveneers
Aug 8, 2014·International Journal of Impotence Research·A M S ZaahkoukM H Yehia
Oct 14, 2016·European Journal of Drug Metabolism and Pharmacokinetics·Khaled S AbdelkawyFawzy Elbarbry
May 12, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dolly Mehta
Jul 14, 2017·American Journal of Physiology. Cell Physiology·Chongxu ZhangIrena Levitan
Mar 25, 2004·The Journal of Biological Chemistry·Jasimuddin Ahamed, Wolfram Ruf
Oct 14, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Elizabeth Le MasterIrena Levitan
Nov 9, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dolly MehtaAsrar B Malik
Jan 20, 2005·American Journal of Physiology. Renal Physiology·Deanne H HryciwPhilip Poronnik
Mar 28, 2007·Journal of Cellular Physiology·Takahiro SuzukiYasufumi Sato

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