Amatruda, Thomas T., III and Gerard, Norma P. and Gerard, Craig and Simon, Melvin I. (1993) Specific Interactions of Chemoattractant Factor Receptors with G-proteins. Journal of Biological Chemistry, 268 (14). pp. 10139-10144. ISSN 0021-9258 http://resolver.caltech.edu/CaltechAUTHORS:20120307-104228505
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Stimulation of leukocytes with chemoattractant ligands activates phospholipid turnover and calcium release, ultimately leading to chemotaxis, degranulation, and the inflammatory response. The leukocyte response to these ligands is transduced by the interaction of transmembrane receptors with GTP-binding regulatory proteins (G-proteins). To examine the mechanisms of signal transduction by these receptors, we transfected cDNA clones encoding the receptors for the active cleavage product of the fifth component of complement (C5a) and platelet-activating factor (PAF) into COS-7 cells, then measured the production of inositol phosphates (IP) in response to stimulation with these chemoattractant ligands. Cells transfected with the C5a receptor showed no increase in IP production when stimulated with ligand (5-120 nM). However, in cells co-transfected with these receptors and with the cDNA for Gα_(16), a G-protein α subunit that is specific to cells of hematopoietic lineage, addition of ligand caused up to a 5-fold increase in IP production. This interaction was specific, as co-transfection of receptors with the G-proteins Gα_q or Gα_(11) did not allow ligand-dependent increase in IP production. In contrast, ligand-dependent activation of IP production was seen in COS cells transfected solely with the PAF receptor. These results indicate that the C5a receptor utilizes signaling pathways distinct from the PAF receptor and suggest that a pertussis toxin-resistant G-protein, Gα_(16), may play a role in the leukocyte response to inflammatory ligands.
|Additional Information:||© 1994 American Society for Biochemistry and Molecular Biology, Inc. Received for publication, February 2, 1993, and in revised form, February 25, 1993. This work was supported by National Institutes of Health Grant GM34236 (to M. I. S.) and HL36162 (to N. G. and C. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely o indicate this fact. We thank Drs. David Steele, Dianqing Wu, and Arieh Katz for providing plasmids, Dr. Mary Territo for the gift of THP-1 cells, Drs. Chang Ho Lee and D. Wu for assistance with inositol phosphate assays, and Cheryl Johnson for help in preparing the manuscript.|
|Official Citation:||T T Amatruda, 3rd, N P Gerard, C Gerard, and M I Simon Specific interactions of chemoattractant factor receptors with G-proteins. J. Biol. Chem. 1993 268: 10139-10144|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Ruth Sustaita|
|Deposited On:||07 Mar 2012 19:32|
|Last Modified:||07 Mar 2012 19:32|
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