QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiménez-Sainz, M. C. Articles by Aragay, A. M. Search for Related Content PubMed PubMed Citation Articles by Jiménez-Sainz, M. C. Articles by Aragay, A. M.

Signaling Pathways for Monocyte Chemoattractant Protein 1-Mediated Extracellular Signal-Regulated Kinase Activation

Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas-Universidad Aútonoma de Madrid, Madrid, Spain (M.C.J.-S., F.M.); and Department of Anatomy and Cell Biology, Faculty of Medicine, University of Bergen, Bergen, Norway (B.F., A.M.A.)

G protein-coupled receptors (GPCRs) initiate diverse down-stream signaling events in response to ligand stimulation, as rapid activation of the extracellular signal-regulated kinase ERK1 and ERK2. The chemokine monocyte chemoattractant protein-1 (MCP-1) is the agonist for several chemokine receptors that belong to the GPCR superfamily, CCR2 being the most important. Stimulation of mitogen-activated protein kinases (MAPKs) by MCP-1 has been implicated in integrin activation and chemotaxis, but the molecular pathways down-stream of the receptors remain unclear. To dissect the cascade of events leading to MAPK activation upon CCR2 receptor stimulation, several specific inhibitors and mutants of signal transduction proteins were used in monocytic cells endogenously expressing CCR2 and/or in human embryonic kidney-293 cells transfected with CCR2B receptors and epitope-tagged ERK1. We show that ERK activation by MCP-1 involves heterotrimeric G_i protein subunits, protein kinase C, phosphoinositide-3-kinase, and Ras. On the other hand, the activity of cytosolic tyrosine kinases, epidermal growth factor receptor transactivation, or variations in intracellular calcium levels are not required for the mitogenic activation elicited by MCP-1. In addition, we find that internalization of CCR2B itself is not necessary for efficient MCP-1-induced activation of ERK, although a dynamin mutant partially inhibits ERK stimulation. These results suggest that different parallel pathways are being activated that lead to the full activation of the mitogen-activated protein kinase cascade and that internalization of other signaling proteins but not of the receptor is required for complete ERK activation.

Address correspondence to: Dr. Anna M. Aragay, Department of Anatomy and Cell Biology, Faculty of Medicine, University of Bergen, N-5009 Bergen, Norway. E-mail: anna.aragay{at}pki.uib.no

This article has been cited by other articles:

				R. Ji, C. M. Lee, L. W. Gonzales, Y. Yang, M. O. Aksoy, P. Wang, E. Brailoiu, N. Dun, M. T. Hurford, and S. G. Kelsen Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1187 - L1196. [Abstract] [Full Text] [PDF]

				P. Pacheco, A. Vieira-de-Abreu, R. N. Gomes, G. Barbosa-Lima, L. B. Wermelinger, C. M. Maya-Monteiro, A. R. Silva, M. T. Bozza, H. C. Castro-Faria-Neto, C. Bandeira-Melo, et al. Monocyte Chemoattractant Protein-1/CC Chemokine Ligand 2 Controls Microtubule-Driven Biogenesis and Leukotriene B4-Synthesizing Function of Macrophage Lipid Bodies Elicited by Innate Immune Response J. Immunol., December 15, 2007; 179(12): 8500 - 8508. [Abstract] [Full Text] [PDF]

				X. Liu, A. M. Das, J. Seideman, D. Griswold, C. N. Afuh, T. Kobayashi, S. Abe, Q. Fang, M. Hashimoto, H. Kim, et al. The CC Chemokine Ligand 2 (CCL2) Mediates Fibroblast Survival through IL-6 Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 121 - 128. [Abstract] [Full Text] [PDF]

				N. F. Neel, L. A. Lapierre, J. R. Goldenring, and A. Richmond RhoB plays an essential role in CXCR2 sorting decisions J. Cell Sci., May 1, 2007; 120(9): 1559 - 1571. [Abstract] [Full Text] [PDF]

				J. H. Sun, B. Yang, D. F. Donnelly, C. Ma, and R. H. LaMotte MCP-1 Enhances Excitability of Nociceptive Neurons in Chronically Compressed Dorsal Root Ganglia J Neurophysiol, November 1, 2006; 96(5): 2189 - 2199. [Abstract] [Full Text] [PDF]

				B. Cat, D. Stuhlmann, H. Steinbrenner, L. Alili, O. Holtkotter, H. Sies, and P. Brenneisen Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species J. Cell Sci., July 1, 2006; 119(13): 2727 - 2738. [Abstract] [Full Text] [PDF]

				M. C. Jimenez-Sainz, C. Murga, A. Kavelaars, M. Jurado-Pueyo, B. F. Krakstad, C. J. Heijnen, F. Mayor Jr., and A. M. Aragay G Protein-coupled Receptor Kinase 2 Negatively Regulates Chemokine Signaling at a Level Downstream from G Protein Subunits Mol. Biol. Cell, January 1, 2006; 17(1): 25 - 31. [Abstract] [Full Text] [PDF]

				F. A. White, J. Sun, S. M. Waters, C. Ma, D. Ren, M. Ripsch, J. Steflik, D. N. Cortright, R. H. LaMotte, and R. J. Miller Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion PNAS, September 27, 2005; 102(39): 14092 - 14097. [Abstract] [Full Text] [PDF]