JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M104442200 on September 17, 2001

J. Biol. Chem., Vol. 276, Issue 51, 47906-47913, December 21, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/51/47906    most recent
M104442200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gratacap, M.-P.
Right arrow Articles by Offermanns, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gratacap, M.-P.
Right arrow Articles by Offermanns, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Differential Regulation of Rho and Rac through Heterotrimeric G-proteins and Cyclic Nucleotides*

Marie-Pierre GratacapDagger §, Bernard Payrastre, Bernhard Nieswandt||, and Stefan OffermannsDagger **

From the Dagger  Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, Heidelberg 69120, Germany,  INSERM, Unité 326, Hôpital Purpan, Toulouse 31059 Cedex, France, and the || Department of Molecular Oncology, General Surgery, Witten/Herdecke University, Wuppertal 42117, Germany

Platelets were used to study the activation of Rho and Rac through G-protein-coupled receptors and its regulation by cyclic nucleotides. The thromboxane A2 (TXA2) mimetic U46619 rapidly activated both small GTPases independently of integrin alpha IIbbeta 3 activation. U46619, which leads to the activation of G12/G13 and Gq did not induce Rac activation in Galpha q-deficient platelets but was able to activate Rho, to stimulate actin polymerization and phosphatidylinositol 4,5-bisphosphate formation, and to induce shape change. Rac activation by U46619 in wild-type platelets could be blocked by chelation of intracellular Ca2+ and was partially sensitive to apyrase and AR-C69931MX, an antagonist of the Gi-coupled ADP receptor. Cyclic AMP, which completely blocks platelet function, inhibited the U46619-induced activation of Gq and G12/G13 as well as of Rac and Rho. In contrast, cGMP, which has no effect on platelet shape change blocked only activation of Gq and Rac. These data demonstrate that Rho and Rac are differentially regulated through heterotrimeric G-proteins. The G12/G13-mediated Rho activation is involved in the shape change response, whereas Rac is activated through Gq and is not required for shape change. Cyclic AMP and cGMP differentially interfere with U46619-induced Rho and Rac activation at least in part by selective effects on the regulation of individual G-proteins through the TXA2 receptor.

* This work was supported in part by the Deutsche Forschungsgemeinschaft and ATCM (INSERM/CNRS).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a postdoctoral scholarship from INSERM (bourse de formation 2000).

** To whom correspondence should be addressed: Tel.: 49-6221-54-8246/7; Fax: 49-6221-54-8549; E-mail: stefan.offermanns@urz.uni-heidelberg.de.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
L. A. Moraes, K. E. Swales, J. A. Wray, A. Damazo, J. M. Gibbins, T. D. Warner, and D. Bishop-Bailey
Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
Blood, May 1, 2007; 109(9): 3741 - 3744.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Offermanns
Activation of Platelet Function Through G Protein-Coupled Receptors
Circ. Res., December 8, 2006; 99(12): 1293 - 1304.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Pandey, P. Goyal, J. R. Bamburg, and W. Siess
Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets
Blood, January 15, 2006; 107(2): 575 - 583.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. J. T. McCarty, M. K. Larson, J. M. Auger, N. Kalia, B. T. Atkinson, A. C. Pearce, S. Ruf, R. B. Henderson, V. L. J. Tybulewicz, L. M. Machesky, et al.
Rac1 Is Essential for Platelet Lamellipodia Formation and Aggregate Stability under Flow
J. Biol. Chem., November 25, 2005; 280(47): 39474 - 39484.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Falet, G. Chang, B. Brohard-Bohn, F. Rendu, and J. H. Hartwig
Integrin {alpha}IIb{beta}3 signals lead cofilin to accelerate platelet actin dynamics
Am J Physiol Cell Physiol, October 1, 2005; 289(4): C819 - C825.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
A. A. Maghazachi
Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells
Pharmacol. Rev., September 1, 2005; 57(3): 339 - 357.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Lian, Y. Wang, J. Draznin, D. Eslin, J. S. Bennett, M. Poncz, D. Wu, and C. S. Abrams
The relative role of PLC{beta} and PI3K{gamma} in platelet activation
Blood, July 1, 2005; 106(1): 110 - 117.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Moers, N. Wettschureck, S. Gruner, B. Nieswandt, and S. Offermanns
Unresponsiveness of Platelets Lacking Both G{alpha}q and G{alpha}13: IMPLICATIONS FOR COLLAGEN-INDUCED PLATELET ACTIVATION
J. Biol. Chem., October 29, 2004; 279(44): 45354 - 45359.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S.-A. Yang, C. L. Carpenter, and C. S. Abrams
Rho and Rho-kinase Mediate Thrombin-induced Phosphatidylinositol 4-Phosphate 5-Kinase Trafficking in Platelets
J. Biol. Chem., October 1, 2004; 279(40): 42331 - 42336.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Endou, K. Iizuka, A. Yoshii, H. Tsukagoshi, T. Ishizuka, K. Dobashi, T. Nakazawa, and M. Mori
8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase
Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L641 - L648.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
A. I. Chernyavsky, J. Arredondo, J. Wess, E. Karlsson, and S. A. Grando
Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors
J. Cell Biol., July 19, 2004; 166(2): 261 - 272.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. A. O. Weernink, K. Meletiadis, S. Hommeltenberg, M. Hinz, H. Ishihara, M. Schmidt, and K. H. Jakobs
Activation of Type I Phosphatidylinositol 4-Phosphate 5-Kinase Isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42
J. Biol. Chem., February 27, 2004; 279(9): 7840 - 7849.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
A. P. SOMLYO and A. V. SOMLYO
Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase
Physiol Rev, October 1, 2003; 83(4): 1325 - 1358.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Vogt, R. Grosse, G. Schultz, and S. Offermanns
Receptor-dependent RhoA Activation in G12/G13-deficient Cells: GENETIC EVIDENCE FOR AN INVOLVEMENT OF Gq/G11
J. Biol. Chem., August 1, 2003; 278(31): 28743 - 28749.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. M. Ellerbroek, K. Wennerberg, and K. Burridge
Serine Phosphorylation Negatively Regulates RhoA in Vivo
J. Biol. Chem., May 23, 2003; 278(21): 19023 - 19031.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. A. Schmidt, L. Scudder, C. E. Devoe, A. Bernards, L. D. Cupit, and W. F. Bahou
IQGAP2 functions as a GTP-dependent effector protein in thrombin-induced platelet cytoskeletal reorganization
Blood, April 15, 2003; 101(8): 3021 - 3028.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
R. Mancini, E. Piccolo, S. Mariggio', B. M. Filippi, C. Iurisci, P. Pertile, C. P. Berrie, and D. Corda
Reorganization of Actin Cytoskeleton by the Phosphoinositide Metabolite Glycerophosphoinositol 4-Phosphate
Mol. Biol. Cell, February 1, 2003; 14(2): 503 - 515.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. M. Manganello, J.-S. Huang, T. Kozasa, T. A. Voyno-Yasenetskaya, and G. C. Le Breton
Protein Kinase A-mediated Phosphorylation of the Galpha 13 Switch I Region Alters the Galpha beta gamma 13-G Protein-coupled Receptor Complex and Inhibits Rho Activation
J. Biol. Chem., January 3, 2003; 278(1): 124 - 130.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. I. Garcia Arguinzonis, A. B. Galler, U. Walter, M. Reinhard, and A. Simm
Increased Spreading, Rac/p21-activated Kinase (PAK) Activity, and Compromised Cell Motility in Cells Deficient in Vasodilator-stimulated Phosphoprotein (VASP)
J. Biol. Chem., November 15, 2002; 277(47): 45604 - 45610.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Gudi, J. C. Chen, D. E. Casteel, T. M. Seasholtz, G. R. Boss, and R. B. Pilz
cGMP-dependent Protein Kinase Inhibits Serum-response Element-dependent Transcription by Inhibiting Rho Activation and Functions
J. Biol. Chem., September 27, 2002; 277(40): 37382 - 37393.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. Falet, K. M. Hoffmeister, R. Neujahr, and J. H. Hartwig
Normal Arp2/3 complex activation in platelets lacking WASp
Blood, August 28, 2002; 100(6): 2113 - 2122.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Chikumi, J. Vazquez-Prado, J.-M. Servitja, H. Miyazaki, and J. S. Gutkind
Potent Activation of RhoA by Galpha q and Gq-coupled Receptors
J. Biol. Chem., July 19, 2002; 277(30): 27130 - 27134.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. M. Schoenwaelder, S. C. Hughan, K. Boniface, S. Fernando, M. Holdsworth, P. E. Thompson, H. H. Salem, and S. P. Jackson
RhoA Sustains Integrin alpha IIbbeta 3 Adhesion Contacts under High Shear
J. Biol. Chem., April 19, 2002; 277(17): 14738 - 14746.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.