This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Adomeit, A.
Right arrow Articles by Liebmann, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adomeit, A.
Right arrow Articles by Liebmann, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 1999, p. 5289-5297, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Bradykinin B2 Receptor-Mediated Mitogen-Activated Protein Kinase Activation in COS-7 Cells Requires Dual Signaling via Both Protein Kinase C Pathway and Epidermal Growth Factor Receptor Transactivation

Antje Adomeit,1 Angela Graness,1 Steffen Gross,2 Klaus Seedorf,3 Reinhard Wetzker,2 and Claus Liebmann1,*

Institute of Biochemistry and Biophysics, Biological and Pharmaceutical Faculty, Friedrich Schiller University, D-07743 Jena,1 and Research Group "Molecular Cell Biology," Medical Faculty, Friedrich Schiller University, D-07747 Jena,2 Germany, and Hagedorn Research Institute, Department of Molecular Signaling, 2820 Gentofte, Denmark3

Received 14 December 1998/Returned for modification 4 February 1999/Accepted 25 March 1999

The signaling routes linking G-protein-coupled receptors to mitogen-activated protein kinase (MAPK) may involve tyrosine kinases, phosphoinositide 3-kinase gamma  (PI3Kgamma ), and protein kinase C (PKC). To characterize the mitogenic pathway of bradykinin (BK), COS-7 cells were transiently cotransfected with the human bradykinin B2 receptor and hemagglutinin-tagged MAPK. We demonstrate that BK-induced activation of MAPK is mediated via the alpha  subunits of a Gq/11 protein. Both activation of Raf-1 and activation of MAPK in response to BK were blocked by inhibitors of PKC as well as of the epidermal growth factor (EGF) receptor. Furthermore, in PKC-depleted COS-7 cells, the effect of BK on MAPK was clearly reduced. Inhibition of PI3-Kgamma or Src kinase failed to diminish MAPK activation by BK. BK-induced translocation and overexpression of PKC isoforms as well as coexpression of inactive or constitutively active mutants of different PKC isozymes provided evidence for a role of the diacylglycerol-sensitive PKCs alpha  and varepsilon  in BK signaling toward MAPK. In addition to PKC activation, BK also induced tyrosine phosphorylation of EGF receptor (transactivation) in COS-7 cells. Inhibition of PKC did not alter BK-induced transactivation, and blockade of EGF receptor did not affect BK-stimulated phosphatidylinositol turnover or BK-induced PKC translocation, suggesting that PKC acts neither upstream nor downstream of the EGF receptor. Comparison of the kinetics of PKC activation and EGF receptor transactivation in response to BK also suggests simultaneous rather than consecutive signaling. We conclude that in COS-7 cells, BK activates MAPK via a permanent dual signaling pathway involving the independent activation of the PKC isoforms alpha  and varepsilon  and transactivation of the EGF receptor. The two branches of this pathway may converge at the level of the Ras-Raf complex.

* Corresponding author. Mailing address: Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, Philosophenweg 12, D-07743 Jena, Germany. Phone: 49-3641-949357. Fax: 49-3641-949352. E-mail: b9licl{at}rZ.uni-jena.de.

Molecular and Cellular Biology, August 1999, p. 5289-5297, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • van der Merwe, J. Q., Hollenberg, M. D., MacNaughton, W. K. (2008). EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G441-G451 [Abstract] [Full Text]  
  • Langlois, S., Nyalendo, C., Di Tomasso, G., Labrecque, L., Roghi, C., Murphy, G., Gingras, D., Beliveau, R. (2007). Membrane-Type 1 Matrix Metalloproteinase Stimulates Cell Migration through Epidermal Growth Factor Receptor Transactivation. Mol Cancer Res 5: 569-583 [Abstract] [Full Text]  
  • Mukhin, Y. V., Gooz, M., Raymond, J. R., Garnovskaya, M. N. (2006). Collagenase-2 and -3 Mediate Epidermal Growth Factor Receptor Transactivation by Bradykinin B2 Receptor in Kidney Cells. J. Pharmacol. Exp. Ther. 318: 1033-1043 [Abstract] [Full Text]  
  • Greco, S, Storelli, C, Marsigliante, S (2006). Protein kinase C (PKC)-{delta}/-{varepsilon} mediate the PKC/Akt-dependent phosphorylation of extracellular signal-regulated kinases 1 and 2 in MCF-7 cells stimulated by bradykinin. J Endocrinol 188: 79-89 [Abstract] [Full Text]  
  • Leeb-Lundberg, L. M. F., Marceau, F., Muller-Esterl, W., Pettibone, D. J., Zuraw, B. L. (2005). International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences. Pharmacol. Rev. 57: 27-77 [Abstract] [Full Text]  
  • Zhao, D., Zhan, Y., Koon, H. W., Zeng, H., Keates, S., Moyer, M. P., Pothoulakis, C. (2004). Metalloproteinase-dependent Transforming Growth Factor-{alpha} Release Mediates Neurotensin-stimulated MAP Kinase Activation in Human Colonic Epithelial Cells. J. Biol. Chem. 279: 43547-43554 [Abstract] [Full Text]  
  • Persson, C., Savenhed, C., Bourdeau, A., Tremblay, M. L., Markova, B., Bohmer, F. D., Haj, F. G., Neel, B. G., Elson, A., Heldin, C.-H., Ronnstrand, L., Ostman, A., Hellberg, C. (2004). Site-Selective Regulation of Platelet-Derived Growth Factor {beta} Receptor Tyrosine Phosphorylation by T-Cell Protein Tyrosine Phosphatase. Mol. Cell. Biol. 24: 2190-2201 [Abstract] [Full Text]  
  • Mukhin, Y. V., Garnovsky, E. A., Ullian, M. E., Garnovskaya, M. N. (2003). Bradykinin B2 Receptor Activates Extracellular Signal-Regulated Protein Kinase in mIMCD-3 Cells via Epidermal Growth Factor Receptor Transactivation. J. Pharmacol. Exp. Ther. 304: 968-977 [Abstract] [Full Text]  
  • Piiper, A., Elez, R., You, S.-J., Kronenberger, B., Loitsch, S., Roche, S., Zeuzem, S. (2003). Cholecystokinin Stimulates Extracellular Signal-regulated Kinase through Activation of the Epidermal Growth Factor Receptor, Yes, and Protein Kinase C. SIGNAL AMPLIFICATION AT THE LEVEL OF Raf BY ACTIVATION OF PROTEIN KINASE Cepsilon. J. Biol. Chem. 278: 7065-7072 [Abstract] [Full Text]  
  • McCole, D. F., Keely, S. J., Coffey, R. J., Barrett, K. E. (2002). Transactivation of the Epidermal Growth Factor Receptor in Colonic Epithelial Cells by Carbachol Requires Extracellular Release of Transforming Growth Factor-alpha. J. Biol. Chem. 277: 42603-42612 [Abstract] [Full Text]  
  • Smit, M. J., Verzijl, D., Casarosa, P., Navis, M., Timmerman, H., Leurs, R. (2002). Kaposi's Sarcoma-Associated Herpesvirus-Encoded G Protein-Coupled Receptor ORF74 Constitutively Activates p44/p42 MAPK and Akt via Gi and Phospholipase C-Dependent Signaling Pathways. J. Virol. 76: 1744-1752 [Abstract] [Full Text]  
  • Hanke, S., Nurnberg, B., Groll, D. H., Liebmann, C. (2001). Cross Talk between beta -Adrenergic and Bradykinin B2 Receptors Results in Cooperative Regulation of Cyclic AMP Accumulation and Mitogen-Activated Protein Kinase Activity. Mol. Cell. Biol. 21: 8452-8460 [Abstract] [Full Text]  
  • Peavy, R. D., Chang, M. S. S., Sanders-Bush, E., Conn, P. J. (2001). Metabotropic Glutamate Receptor 5-Induced Phosphorylation of Extracellular Signal-Regulated Kinase in Astrocytes Depends on Transactivation of the Epidermal Growth Factor Receptor. J. Neurosci. 21: 9619-9628 [Abstract] [Full Text]  
  • Keates, S., Sougioultzis, S., Keates, A. C., Zhao, D., Peek, R. M. Jr., Shaw, L. M., Kelly, C. P. (2001). cag+ Helicobacter pylori Induce Transactivation of the Epidermal Growth Factor Receptor in AGS Gastric Epithelial Cells. J. Biol. Chem. 276: 48127-48134 [Abstract] [Full Text]  
  • Blaukat, A., Barac, A., Cross, M. J., Offermanns, S., Dikic, I. (2000). G Protein-Coupled Receptor-Mediated Mitogen-Activated Protein Kinase Activation through Cooperation of Galpha q and Galpha i Signals. Mol. Cell. Biol. 20: 6837-6848 [Abstract] [Full Text]  
  • Carpenter, G. (1999). Employment of the Epidermal Growth Factor Receptor in Growth Factor-Independent Signaling Pathways. JCB 146: 697-702 [Full Text]  
  • van Rossum, G. S. A. T., Klooster, R., van den Bosch, H., Verkleij, A. J., Boonstra, J. (2001). Phosphorylation of p42/44MAPK by Various Signal Transduction Pathways Activates Cytosolic Phospholipase A2 to Variable Degrees. J. Biol. Chem. 276: 28976-28983 [Abstract] [Full Text]  
  • Thuringer, D., Maulon, L., Frelin, C. (2002). Rapid Transactivation of the Vascular Endothelial Growth Factor Receptor KDR/Flk-1 by the Bradykinin B2 Receptor Contributes to Endothelial Nitric-oxide Synthase Activation in Cardiac Capillary Endothelial Cells. J. Biol. Chem. 277: 2028-2032 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»