HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanders, S. K. Articles by Hunt, S. W. Search for Related Content PubMed PubMed Citation Articles by Sanders, S. K. Articles by Hunt, S. W., III

Functional Differences Between Monocyte Chemotactic Protein-1 Receptor A and Monocyte Chemotactic Protein-1 Receptor B Expressed in a Jurkat T Cell

Sheila K. Sanders^1,*, Sheila M. Crean, Peter A. Boxer, Debra Kellner^*, Gregory J. LaRosa^§ and Stephen W. Hunt, III^*

Departments of ^* Molecular Biology, Cancer Therapeutics, and Neuroscience, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, MI 48105; and ^§ Millennium Pharmaceuticals, Inc., Cambridge, MA 02142

The monocyte chemotactic protein-1 (MCP-1) receptor (MCP-1R) is expressed on monocytes, a subpopulation of memory T lymphocytes, and basophils. Two alternatively spliced forms of MCP-1R, CCR2A and CCR2B, exist and differ only in their carboxyl-terminal tails. To determine whether CCR2A and CCR2B receptors function similarly, Jurkat T cells were stably transfected with plasmids encoding the human CCR2A or CCR2B gene. Nanomolar concentrations of MCP-1 induced chemotaxis in the CCR2B transfectants that express high, intermediate, and low levels of MCP-1R. Peak chemotactic activity was shifted to the right as receptor number decreased. Five-fold more MCP-1 was required to initiate chemotaxis of the CCR2A low transfectant, but the peak of chemotaxis was similar for the CCR2A and CCR2B transfectants expressing similar numbers of receptors. MCP-1-induced chemotaxis was sensitive to pertussis toxin, implying that both CCR2A and CCR2B are G_i protein coupled. MCP-1 induced a transient Ca²⁺ flux in the CCR2B transfectant that was partially sensitive to pertussis toxin. In contrast, MCP-1 did not induce Ca²⁺ flux in the CCR2A transfectant. Since MCP-1 can stimulate chemotaxis of the CCR2A transfectant without inducing Ca²⁺ mobilization, Ca²⁺ flux may not be required for MCP-1-induced chemotaxis in the Jurkat transfectants. These results indicate that functional differences exist between the CCR2A and CCR2B transfectants that can be attributed solely to differences in the carboxyl-terminal tail.

This article has been cited by other articles:

				J. Park, D.-R. Ryu, J. J. Li, D.-S. Jung, S.-J. Kwak, S. H. Lee, T.-H. Yoo, S. H. Han, J. E. Lee, D. K. Kim, et al. MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells Am J Physiol Renal Physiol, September 1, 2008; 295(3): F749 - F757. [Abstract] [Full Text] [PDF]

				M. Gouwy, S. Struyf, J. Catusse, P. Proost, and J. Van Damme Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration J. Leukoc. Biol., July 1, 2004; 76(1): 185 - 194. [Abstract] [Full Text] [PDF]

				S.-A. Kellermann and L. M. McEvoy The Peyer's Patch Microenvironment Suppresses T Cell Responses to Chemokines and Other Stimuli J. Immunol., July 15, 2001; 167(2): 682 - 690. [Abstract] [Full Text] [PDF]