Direct regulation of p190RhoGEF by activated Rho and Rac GTPases

Dada, Olugbenga; Gutowski, Stephen; Brautigam, Chad A.; Chen, Zhe; Sternweis, Paul C.

doi:10.1016/j.jsb.2017.11.014

Title: Direct regulation of p190RhoGEF by activated Rho and Rac GTPases

Journal Article · Tue Nov 28 00:00:00 EST 2017 · Journal of Structural Biology

DOI:https://doi.org/10.1016/j.jsb.2017.11.014· OSTI ID:1511722

Dada, Olugbenga ^[1]; Gutowski, Stephen ^[1]; Brautigam, Chad A. ^[1]; Chen, Zhe ^[1]; Sternweis, Paul C. ^[1]

Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

Rho family GTPases regulate a wide range of cellular processes. This includes cellular dynamics where three subfamilies, Rho, Rac, and Cdc42, are known to regulate cell shape and migration though coordinate action. Activation of Rho proteins largely depends on Rho Guanine nucleotide Exchange Factors (RhoGEFs) through a catalytic Dbl homology (DH) domain linked to a pleckstrin homology (PH) domain that subserves various functions. The PH domains from Lbc RhoGEFs, which specifically activate RhoA, have been shown to bind to activated RhoA. Here, p190RhoGEF is shown to also bind Rac1·GTP. Crystal structures reveal that activated Rac1 and RhoA use their effector-binding surfaces to associate with the same hydrophobic surface on the PH domain. Additionally, both activated RhoA and Rac1 can stimulate exchange of nucleotide on RhoA by localization of p190RhoGEF to its substrate, RhoA·GDP, in vitro. The binding of activated RhoA provides a mechanism for positive feedback regulation as previously proposed for the family of Lbc RhoGEFs. In contrast, the novel interaction between activated Rac1 and p190RhoGEF reveals a potential mechanism for cross-talk regulation where Rac can directly effect stimulation of RhoA. The greater capacity of Rac1 to stimulate p190RhoGEF among the Lbc RhoGEFs suggests functional specialization.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: GM31954; AC02-06CH11357

OSTI ID:: 1511722

Alternate ID(s):: OSTI ID: 1898932

Journal Information:: Journal of Structural Biology, Vol. 202, Issue 1; ISSN 1047-8477

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 6 works

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References (42)

PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells Aittaleb, Mohamed; Gao, Guang; Evelyn, Chris R. Cellular Signalling, Vol. 21, Issue 11 https://doi.org/10.1016/j.cellsig.2009.06.003	journal	November 2009
The Protein Data Bank Berman, H. M. Nucleic Acids Research, Vol. 28, Issue 1 https://doi.org/10.1093/nar/28.1.235	journal	January 2000
GEFs and GAPs: Critical Elements in the Control of Small G Proteins Bos, Johannes L.; Rehmann, Holger; Wittinghofer, Alfred Cell, Vol. 129, Issue 5 https://doi.org/10.1016/j.cell.2007.05.018	journal	June 2007
p190RhoGEF Binds to a Destabilizing Element in the 3′ Untranslated Region of Light Neurofilament Subunit mRNA and Alters the Stability of the Transcript Cañete-Soler, Rafaela; Wu, Junhua; Zhai, Jinbin Journal of Biological Chemistry, Vol. 276, Issue 34 https://doi.org/10.1074/jbc.M104104200	journal	August 2001
Regulated Localization Is Sufficient for Hormonal Control of Regulator of G Protein Signaling Homology Rho Guanine Nucleotide Exchange Factors (RH-RhoGEFs) Carter, Angela M.; Gutowski, Stephen; Sternweis, Paul C. Journal of Biological Chemistry, Vol. 289, Issue 28 https://doi.org/10.1074/jbc.M114.564930	journal	May 2014
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Activated RhoA Binds to the Pleckstrin Homology (PH) Domain of PDZ-RhoGEF, a Potential Site for Autoregulation Chen, Zhe; Medina, Frank; Liu, Mu-ya Journal of Biological Chemistry, Vol. 285, Issue 27 https://doi.org/10.1074/jbc.M110.122549	journal	April 2010
Recognition of the Activated States of Gα13 by the rgRGS Domain of PDZRhoGEF Chen, Zhe; Singer, William D.; Danesh, Shahab M. Structure, Vol. 16, Issue 10 https://doi.org/10.1016/j.str.2008.07.009	journal	October 2008
Pleckstrin Homology Domain-mediated Activation of the Rho-specific Guanine Nucleotide Exchange Factor Dbs by Rac1 Cheng, Li; Mahon, Gwendolyn M.; Kostenko, Elena V. Journal of Biological Chemistry, Vol. 279, Issue 13 https://doi.org/10.1074/jbc.M313099200	journal	March 2004
Regulation of Small GTPases by GEFs, GAPs, and GDIs Cherfils, Jacqueline; Zeghouf, Mahel Physiological Reviews, Vol. 93, Issue 1 https://doi.org/10.1152/physrev.00003.2012	journal	January 2013
Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine Phosphorylation Chikumi, Hiroki; Fukuhara, Shigetomo; Gutkind, J. Silvio Journal of Biological Chemistry, Vol. 277, Issue 14 https://doi.org/10.1074/jbc.M108504200	journal	April 2002
Sedimentation Velocity Analysis of Heterogeneous Protein-Protein Interactions: Sedimentation Coefficient Distributions c(s) and Asymptotic Boundary Profiles from Gilbert-Jenkins Theory Dam, Julie; Schuck, Peter Biophysical Journal, Vol. 89, Issue 1 https://doi.org/10.1529/biophysj.105.059584	journal	July 2005
A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin Dubash, Adi D.; Wennerberg, Krister; García-Mata, Rafael Journal of Cell Science, Vol. 120, Issue 22 https://doi.org/10.1242/jcs.003806	journal	November 2007
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Rho GEF Lsc is required for normal polarization, migration, and adhesion of formyl-peptide–stimulated neutrophils Francis, Sanjeev A.; Shen, Xun; Young, Jeffrey B. Blood, Vol. 107, Issue 4 https://doi.org/10.1182/blood-2005-03-1164	journal	February 2006
Calculation of Hydrodynamic Properties of Globular Proteins from Their Atomic-Level Structure García de la Torre, José; Huertas, María L.; Carrasco, Beatriz Biophysical Journal, Vol. 78, Issue 2 https://doi.org/10.1016/S0006-3495(00)76630-6	journal	February 2000
Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology Gebbink, Martijn F. B. G.; Kranenburg, Onno; Poland, Mieke Journal of Cell Biology, Vol. 137, Issue 7 https://doi.org/10.1083/jcb.137.7.1603	journal	June 1997
Rho protein crosstalk: another social network? Guilluy, Christophe; Garcia-Mata, Rafael; Burridge, Keith Trends in Cell Biology, Vol. 21, Issue 12 https://doi.org/10.1016/j.tcb.2011.08.002	journal	December 2011
Genetic Deletion of Rac1 GTPase Reveals Its Critical Role in Actin Stress Fiber Formation and Focal Adhesion Complex Assembly Guo, Fukun; Debidda, Marcella; Yang, Linda Journal of Biological Chemistry, Vol. 281, Issue 27 https://doi.org/10.1074/jbc.M603508200	journal	July 2006
FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts Iwanicki, Marcin P.; Vomastek, Tomas; Tilghman, Robert W. Journal of Cell Science, Vol. 121, Issue 6 https://doi.org/10.1242/jcs.020941	journal	March 2008
Mechanistic Insights into Specificity, Activity, and Regulatory Elements of the Regulator of G-protein Signaling (RGS)-containing Rho-specific Guanine Nucleotide Exchange Factors (GEFs) p115, PDZ-RhoGEF (PRG), and Leukemia-associated RhoGEF (LARG) Jaiswal, Mamta; Gremer, Lothar; Dvorsky, Radovan Journal of Biological Chemistry, Vol. 286, Issue 20 https://doi.org/10.1074/jbc.M111.226431	journal	May 2011
High-Precision Isothermal Titration Calorimetry with Automated Peak-Shape Analysis Keller, Sandro; Vargas, Carolyn; Zhao, Huaying Analytical Chemistry, Vol. 84, Issue 11 https://doi.org/10.1021/ac3007522	journal	June 2012
PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility Lim, Yangmi; Lim, Ssang-Taek; Tomar, Alok Journal of Cell Biology, Vol. 180, Issue 1 https://doi.org/10.1083/jcb.200708194	journal	January 2008
RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration Lin, Hong; Zhai, Jinbin; Schlaepfer, William W. Human Molecular Genetics, Vol. 14, Issue 23 https://doi.org/10.1093/hmg/ddi392	journal	October 2005
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Activated RhoA Is a Positive Feedback Regulator of the Lbc Family of Rho Guanine Nucleotide Exchange Factor Proteins Medina, Frank; Carter, Angela M.; Dada, Olugbenga Journal of Biological Chemistry, Vol. 288, Issue 16 https://doi.org/10.1074/jbc.M113.450056	journal	March 2013
Interaction of c-Jun Amino-terminal Kinase Interacting Protein-1 with p190 rhoGEF and Its Localization in Differentiated Neurons Meyer, Debra; Liu, Albert; Margolis, Ben Journal of Biological Chemistry, Vol. 274, Issue 49 https://doi.org/10.1074/jbc.274.49.35113	journal	December 1999
Rgnef (p190RhoGEF) Knockout Inhibits RhoA Activity, Focal Adhesion Establishment, and Cell Motility Downstream of Integrins Miller, Nichol L. G.; Lawson, Christine; Chen, Xiao Lei PLoS ONE, Vol. 7, Issue 5 https://doi.org/10.1371/journal.pone.0037830	journal	May 2012
A non-canonical role for Rgnef (p190RhoGEF) in promoting integrin-stimulated focal adhesion kinase activation Miller, Nichol L. G.; Lawson, Christine; Kleinschmidt, Elizabeth G. Journal of Cell Science https://doi.org/10.1242/jcs.135509	journal	January 2013
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors Rossman, Kent L.; Der, Channing J.; Sondek, John Nature Reviews Molecular Cell Biology, Vol. 6, Issue 2 https://doi.org/10.1038/nrm1587	journal	February 2005
Toward understanding RhoGTPase specificity: structure, function and local activation Schaefer, Antje; Reinhard, Nathalie R.; Hordijk, Peter L. Small GTPases, Vol. 5, Issue 2 https://doi.org/10.4161/21541248.2014.968004	journal	April 2014
Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling Schuck, Peter Biophysical Journal, Vol. 78, Issue 3 https://doi.org/10.1016/S0006-3495(00)76713-0	journal	March 2000
On the analysis of protein self-association by sedimentation velocity analytical ultracentrifugation Schuck, Peter Analytical Biochemistry, Vol. 320, Issue 1 https://doi.org/10.1016/S0003-2697(03)00289-6	journal	September 2003
Quantitative Analysis of the Effect of Phosphoinositide Interactions on the Function of Dbl Family Proteins Snyder, Jason T.; Rossman, Kent L.; Baumeister, Mark A. Journal of Biological Chemistry, Vol. 276, Issue 49 https://doi.org/10.1074/jbc.M106731200	journal	December 2001
Characterization of p190RhoGEF, A RhoA-specific Guanine Nucleotide Exchange Factor That Interacts with Microtubules van Horck, Francis P. G.; Ahmadian, M. Reza; Haeusler, Lars C. Journal of Biological Chemistry, Vol. 276, Issue 7 https://doi.org/10.1074/jbc.M003839200	journal	February 2001
Regulation of the DH–PH tandem of guanine nucleotide exchange factor for Rho GTPases by phosphoinositides Viaud, Julien; Gaits-Iacovoni, Frédérique; Payrastre, Bernard Advances in Biological Regulation, Vol. 52, Issue 2 https://doi.org/10.1016/j.jbior.2012.04.001	journal	May 2012
p190RhoGEF (Rgnef) Promotes Colon Carcinoma Tumor Progression via Interaction with Focal Adhesion Kinase Yu, Hong-Gang; Nam, Ju-Ock; Miller, Nichol L. G. Cancer Research, Vol. 71, Issue 2 https://doi.org/10.1158/0008-5472.CAN-10-2894	journal	January 2011
Direct Interaction of Focal Adhesion Kinase with p190RhoGEF Zhai, Jinbin; Lin, Hong; Nie, Zhenying Journal of Biological Chemistry, Vol. 278, Issue 27 https://doi.org/10.1074/jbc.M302381200	journal	July 2003
Identification of a Novel Interaction of 14-3-3 with p190RhoGEF Zhai, Jinbin; Lin, Hong; Shamim, Mohammad Journal of Biological Chemistry, Vol. 276, Issue 44 https://doi.org/10.1074/jbc.M107709200	journal	November 2001
SEDPHAT – A platform for global ITC analysis and global multi-method analysis of molecular interactions Zhao, Huaying; Piszczek, Grzegorz; Schuck, Peter Methods, Vol. 76 https://doi.org/10.1016/j.ymeth.2014.11.012	journal	April 2015

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