PMID- 9169480 OWN - NLM STAT- MEDLINE DCOM- 19970626 LR - 20220311 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 272 IP - 23 DP - 1997 Jun 6 TI - The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. PG - 15036-42 AB - Thymus and activation-regulated chemokine (TARC) is a recently identified CC chemokine that is expressed constitutively in thymus and transiently in stimulated peripheral blood mononuclear cells. TARC functions as a selective chemoattractant for T cells that express a class of receptors binding TARC with high affinity and specificity. To identify the receptor for TARC, we produced TARC as a fusion protein with secreted alkaline phosphatase (SEAP) and used it for specific binding. By stably transfecting five orphan receptors and five known CC chemokine receptors (CCR1 to -5) into K562 cells, we found that TARC-SEAP bound selectively to cells expressing CCR4. TARC-SEAP also bound to K562 cells stably expressing CCR4 with a high affinity (Kd = 0.5 nM). Only TARC and not five other CC chemokines (MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cells expressed and secreted), MIP-1alpha (macrophage inflammatory protein-1alpha), MIP-1beta, and LARC (liver and activation-regulated chemokine)) competed with TARC-SEAP for binding to CCR4. TARC but not RANTES or MIP-1alpha induced migration and calcium mobilization in 293/EBNA-1 cells stably expressing CCR4. K562 cells stably expressing CCR4 also responded to TARC in a calcium mobilization assay. Northern blot analysis revealed that CCR4 mRNA was expressed strongly in human T cell lines and peripheral blood T cells but not in B cells, natural killer cells, monocytes, or granulocytes. Taken together, TARC is a specific functional ligand for CCR4, and CCR4 is the specific receptor for TARC selectively expressed on T cells. FAU - Imai, T AU - Imai T AD - Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566, Japan. toshio.imai@shionogi.co.jp FAU - Baba, M AU - Baba M FAU - Nishimura, M AU - Nishimura M FAU - Kakizaki, M AU - Kakizaki M FAU - Takagi, S AU - Takagi S FAU - Yoshie, O AU - Yoshie O LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CCL17 protein, human) RN - 0 (CCR4 protein, human) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CCL5) RN - 0 (Chemokines) RN - 0 (Chemokines, CC) RN - 0 (Receptors, CCR4) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Cytokine) RN - 0 (Recombinant Fusion Proteins) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - SY7Q814VUP (Calcium) SB - IM MH - Alkaline Phosphatase/biosynthesis MH - B-Lymphocytes/immunology MH - Binding, Competitive MH - Calcium/metabolism MH - Cell Line MH - Chemokine CCL17 MH - Chemokine CCL5/pharmacology MH - Chemokines/*metabolism/*pharmacology MH - *Chemokines, CC MH - Chemotaxis MH - Humans MH - Kinetics MH - Polymerase Chain Reaction MH - Receptors, CCR4 MH - *Receptors, Chemokine MH - Receptors, Cytokine/biosynthesis/*metabolism MH - Recombinant Fusion Proteins/biosynthesis/metabolism MH - T-Lymphocytes/*immunology MH - Transfection MH - Tumor Cells, Cultured EDAT- 1997/06/06 00:00 MHDA- 1997/06/06 00:01 CRDT- 1997/06/06 00:00 PHST- 1997/06/06 00:00 [pubmed] PHST- 1997/06/06 00:01 [medline] PHST- 1997/06/06 00:00 [entrez] AID - S0021-9258(19)62495-6 [pii] AID - 10.1074/jbc.272.23.15036 [doi] PST - ppublish SO - J Biol Chem. 1997 Jun 6;272(23):15036-42. doi: 10.1074/jbc.272.23.15036.