PMID- 8702980 OWN - NLM STAT- MEDLINE DCOM- 19961010 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 271 IP - 36 DP - 1996 Sep 6 TI - Differential regulation of G-protein-mediated signaling by chemokine receptors. PG - 21814-9 AB - Monocyte chemoattractant protein-1 (MCP-1) is a member of a family of chemotactic cytokines that induce directed migration of leukocytes via activation of seven-transmembrane domain receptors. To identify G-proteins that couple to the two forms of the MCP-1 receptor, as well as to related chemokine receptors, we have performed cotransfection experiments in mammalian cells. In COS-7 cells, the type A and type B MCP-1 receptors coupled to Galphai, Galphaq, and Galpha16, whereas the macrophage inflammatory protein-1alpha/RANTES (regulated on activation, normal T cell-expressed and secreted) receptor (C-CR1) coupled to Galphai and Galphaq but failed to couple to Galpha16. In HEK-293 cells, however, the MCP-1 receptors and C-CR1 coupled to Galphaq but failed to couple to Galpha16. In contrast, the interleukin-8 and C5a receptors did not couple to Galphaq in either COS-7 or HEK-293 cells but did couple to Galpha16. Exchange of intracellular loops between the MCP-1 and interleukin-8 receptors to create chimeric receptors revealed that the third loop of the MCP-1 receptor accounted for virtually all of the coupling to Galphaq. We conclude that the MCP-1 and related chemokine receptors couple to multiple G-proteins, that coupling is cell type-specific, and that the third intracellular loop of the C-C type receptors mediates Galphaq coupling. FAU - Arai, H AU - Arai H AD - Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141-9100, USA. FAU - Charo, I F AU - Charo IF LA - eng GR - HL52773/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antigens, CD) RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Inositol Phosphates) RN - 0 (Phosphatidylinositols) RN - 0 (Receptor, Anaphylatoxin C5a) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Complement) RN - 0 (Receptors, Cytokine) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-8A) RN - 0 (Virulence Factors, Bordetella) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Amino Acid Sequence MH - Antigens, CD/metabolism MH - Cell Line MH - Chemokine CCL2/*metabolism MH - Chemokine CCL5/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - GTP-Binding Proteins/*metabolism MH - Humans MH - Hydrolysis MH - Inositol Phosphates/metabolism MH - Molecular Sequence Data MH - Phosphatidylinositols/metabolism MH - Protein Structure, Secondary MH - Receptor, Anaphylatoxin C5a MH - Receptors, CCR2 MH - *Receptors, Chemokine MH - Receptors, Complement/metabolism MH - Receptors, Cytokine/*metabolism MH - Receptors, Interleukin/metabolism MH - Receptors, Interleukin-8A MH - *Signal Transduction MH - Structure-Activity Relationship MH - Substrate Specificity MH - Virulence Factors, Bordetella/pharmacology MH - beta-Adrenergic Receptor Kinases EDAT- 1996/09/06 00:00 MHDA- 1996/09/06 00:01 CRDT- 1996/09/06 00:00 PHST- 1996/09/06 00:00 [pubmed] PHST- 1996/09/06 00:01 [medline] PHST- 1996/09/06 00:00 [entrez] AID - S0021-9258(19)61864-8 [pii] AID - 10.1074/jbc.271.36.21814 [doi] PST - ppublish SO - J Biol Chem. 1996 Sep 6;271(36):21814-9. doi: 10.1074/jbc.271.36.21814.