Plasma membrane association of p63 Rho guanine nucleotide exchange factor (p63RhoGEF) is mediated by palmitoylation and is required for basal activity in cells

The Journal of Biological Chemistry
Mohamed AittalebJohn J G Tesmer


Activation of G protein-coupled receptors at the cell surface leads to the activation or inhibition of intracellular effector enzymes, which include various Rho guanine nucleotide exchange factors (RhoGEFs). RhoGEFs activate small molecular weight GTPases at the plasma membrane (PM). Many of the known G protein-coupled receptor-regulated RhoGEFs are found in the cytoplasm of unstimulated cells, and PM recruitment is a critical aspect of their regulation. In contrast, p63RhoGEF, a Gα(q)-regulated RhoGEF, appears to be constitutively localized to the PM. The objective of this study was to determine the molecular basis for the localization of p63RhoGEF and the impact of its subcellular localization on its regulation by Gα(q). Herein, we show that the pleckstrin homology domain of p63RhoGEF is not involved in its PM targeting. Instead, a conserved string of cysteines (Cys-23/25/26) at the N terminus of the enzyme is palmitoylated and required for membrane localization and full basal activity in cells. Conversion of these residues to serine relocates p63RhoGEF from the PM to the cytoplasm, diminishes its basal activity, and eliminates palmitoylation. The activity of palmitoylation-deficient p63RhoGEF can be rescued by targeting to t...Continue Reading


Nov 30, 2013·Trends in Pharmacological Sciences·Angeline M LyonJohn J G Tesmer
Sep 19, 2012·Biochimica Et Biophysica Acta·Sunny Yang XiangJoan Heller Brown
Aug 21, 2012·Trends in Cardiovascular Medicine·Ko Momotani, Avril V Somlyo
Oct 6, 2015·Scientific Reports·Jakobus van UnenJoachim Goedhart
Dec 5, 2013·The Biochemical Journal·Eva-Lisa BodmannMoritz Bünemann
Oct 27, 2010·PLoS Computational Biology·Brenda R S TempleAlan M Jones
Sep 24, 2015·Journal of Molecular and Cellular Cardiology·Anita OngherthSusanne Lutz
Apr 3, 2015·Physiological Reviews·Luke H Chamberlain, Michael J Shipston


Jan 5, 1996·The Journal of Biological Chemistry·John R HeplerA G Gilman
Jun 26, 1998·Science·Tohru KozasaP C Sternweis
Aug 6, 2000·The Biochemical Journal·Mark A Lemmon, K M Ferguson
Aug 17, 2002·The Journal of Biological Chemistry·Valerie PerrotJ Silvio Gutkind
Aug 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jennifer AurandtKun-Liang Guan
Jan 15, 2004·Biology of the Cell·J-M BellangerA Debant
Jan 28, 2004·Cell·Keith Burridge, Krister Wennerberg
Jun 11, 2004·Annual Review of Biochemistry·Jessica E Smotrys, Maurine E Linder
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
Jun 2, 2007·Cell·Johannes L BosAlfred Wittinghofer
Jun 15, 2007·Biochemistry·Yannick MarrariPhilip B Wedegaertner
Jun 20, 2007·The Journal of Biological Chemistry·Mariangela ChisariNarasimhan Gautam
Aug 19, 2007·Molecular Cancer Therapeutics·Chris R EvelynRichard R Neubig
Sep 15, 2007·Advances in Protein Chemistry·Stephen R SprangXinlin Du
Sep 15, 2007·Advances in Protein Chemistry·Paul C SternweisWilliam D Singer
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Mark A Lemmon
Mar 6, 2008·Journal of Cellular Biochemistry·Bruno H MeyerSandra Siehler
Jul 11, 2008·The Journal of Biological Chemistry·Patrick J RobertsChanning J Der
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Sarah J Heasman, Anne J Ridley
Nov 13, 2008·Molecular and Cellular Biology·Ryouhei TsutsumiMasaki Fukata
Dec 17, 2008·The Journal of Biological Chemistry·Nobuchika SuzukiTohru Kozasa
Jan 13, 2009·Nature Methods·Brent R Martin, Benjamin F Cravatt
Feb 13, 2009·Neuro-Signals·Nobuchika SuzukiTohru Kozasa
Feb 20, 2009·British Journal of Pharmacology·Sandra Siehler
Mar 3, 2009·Cellular Signalling·Raja BhattacharyyaPhilip B Wedegaertner
Mar 14, 2009·Journal of the American Chemical Society·Guillaume CharronHoward C Hang
Nov 3, 2009·Molecular Pharmacology·Mohamed AittalebJohn J G Tesmer
Mar 11, 2010·Cellular Signalling·Aruna ShankaranarayananJohn J G Tesmer
May 1, 2010·The Journal of Biological Chemistry·Zhe ChenPaul C Sternweis
Jul 29, 2010·Molecular Pharmacology·Marykate CrouthamelPhilip B Wedegaertner
Dec 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ilya LeventalKai Simons

Related Concepts

Establishment and Maintenance of Localization
Carnitine Palmitoyl Transferase 2 Deficiency
HEK293 Cells
ARHGEF28 gene
Enzymes, antithrombotic
G-Protein-Coupled Receptors
PH Domain
Tertiary Protein Structure
Type C Phospholipases

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.