help button home button Am J Pathol Angiogenesis Meeting
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cybulsky, A. V.
Right arrow Articles by McTavish, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cybulsky, A. V.
Right arrow Articles by McTavish, A. J.
(American Journal of Pathology. 1999;155:1701-1711.)
© 1999 American Society for Investigative Pathology

Regular Articles

Complement C5b-9 Induces Receptor Tyrosine Kinase Transactivation in Glomerular Epithelial Cells

Andrey V. Cybulsky, Tomoko Takano, Joan Papillon and Alison J. McTavish

From the Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada

In the passive Heymann nephritis (PHN) model of membranous nephropathy, C5b-9 induces glomerular epithelial cell (GEC) injury and proteinuria, which is partially mediated via production of eicosanoids. Using rat GEC in culture, we demonstrated that sublytic C5b-9 induced tyrosine phosphorylation of the epidermal growth factor receptor (EGF-R), Neu, fibroblast growth factor receptor-2, and hepatocyte growth factor receptor. In addition, C5b-9 stimulated increases in tyrosine204 phosphorylation of extracellular signal-regulated kinase-2 (ERK2), as well as free [3H]arachidonic acid (AA) and prostaglandin E2 (PGE2). Phosphorylated EGF-R bound the adaptor protein, Grb2, and the EGF-R-selective tyrphostin, AG1478, blocked the C5b-9-induced ERK2 phosphorylation, [3H]AA release, and PGE2 production by 45 to 65%, supporting a functional role for EGF-R kinase in mediating the activation of these pathways. Glomeruli isolated from rats with PHN demonstrated increases in ERK2 tyrosine204 phosphorylation and PGE2 production, as compared with glomeruli from control rats, and these increases were partially inhibited with AG1478. Thus, C5b-9 induces transactivation of receptor tyrosine kinases, in association with ERK2 activation, AA release, and PGE2 production in cultured GEC and glomerulonephritis in vivo. Transactivated tyrosine kinases may serve as scaffolds for assembly and/or activation of proteins, which then lead to activation of the ERK2 cascade and AA metabolism.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
N. S. Bora, S. Kaliappan, P. Jha, Q. Xu, B. Sivasankar, C. L. Harris, B. P. Morgan, and P. S. Bora
CD59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-Type Age-Related Macular Degeneration
J. Immunol., February 1, 2007; 178(3): 1783 - 1790.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. V. Cybulsky, R. J. Quigg, and D. J. Salant
Experimental membranous nephropathy redux
Am J Physiol Renal Physiol, October 1, 2005; 289(4): F660 - F671.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, and J. Guillemette
Activation of the extracellular signal-regulated kinase by complement C5b-9
Am J Physiol Renal Physiol, September 1, 2005; 289(3): F593 - F603.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. V. Cybulsky, T. Takano, J. Papillon, and K. Bijian
Role of the Endoplasmic Reticulum Unfolded Protein Response in Glomerular Epithelial Cell Injury
J. Biol. Chem., July 1, 2005; 280(26): 24396 - 24403.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. S. Bora, J.-H. Sohn, J. M. C. Cruz, P. Jha, H. Nishihori, Y. Wang, S. Kaliappan, H. J. Kaplan, and N. S. Bora
Role of Complement and Complement Membrane Attack Complex in Laser-Induced Choroidal Neovascularization
J. Immunol., January 1, 2005; 174(1): 491 - 497.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. Turnberg, M. Botto, M. Lewis, W. Zhou, S. H. Sacks, B. P. Morgan, M. J. Walport, and H. T. Cook
CD59a Deficiency Exacerbates Ischemia-Reperfusion Injury in Mice
Am. J. Pathol., September 1, 2004; 165(3): 825 - 832.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. V. Cybulsky, T. Takano, J. Papillon, A. Khadir, K. Bijian, and L. Le Berre
The actin cytoskeleton facilitates complement-mediated activation of cytosolic phospholipase A2
Am J Physiol Renal Physiol, March 1, 2004; 286(3): F466 - F476.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Bijian, T. Takano, J. Papillon, A. Khadir, and A. V. Cybulsky
Extracellular matrix regulates glomerular epithelial cell survival and proliferation
Am J Physiol Renal Physiol, February 1, 2004; 286(2): F255 - F266.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Turnberg, M. Botto, J. Warren, B. P. Morgan, Mark. J. Walport, and H. T. Cook
CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice
J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2271 - 2279.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. V. Cybulsky, T. Takano, J. Papillon, A. Khadir, J. Liu, and H. Peng
Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells
J. Biol. Chem., October 25, 2002; 277(44): 41342 - 41351.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.