Details

Autor(en) / Beteiligte

• Tian, Yaji
• New, David C.
• Yung, Lisa Y.
• Allen, Rodger A.
• Slocombe, Patrick M.
• Twomey, Breda M.
• Lee, Maggie M. K.
• Wong, Yung H.

Titel

Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα 14‐coupled pathways

Ist Teil von

• European journal of immunology, 2004-03, Vol.34 (3), p.785-795

Ort / Verlag

Weinheim: WILEY‐VCH Verlag

Erscheinungsjahr

2004

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Chemokines regulate the chemotaxis, development, and differentiation of many cell types enabling the regulation of routine immunosurveillance and immunological adaptation. CC chemokine receptor 1 (CCR1) is the target of 11 chemokines. This promiscuity of receptor‐ligand interactions and the potential for functional redundancy has led us to investigate the selective activation of CCR1‐coupled pathways by known CCR1 agonists. Chemokines leukotactin‐1, macrophage inflammatory protein (MIP)‐1α, monocyte chemotactic peptide (MCP)‐3, RANTES, and MIP‐1δ all inhibited adenylyl cyclase activity in cells transiently transfected with CCR1. In contrast, only MIP‐1δ was unable to signal via G14‐, G16‐ or chimeric 16z44‐coupled pathways. In a stable cell line expressing CCR1 and Gα14, all of these five chemokines along with hemofiltrate CC chemokine (HCC)‐1 and myeloid progenitor inhibitory factor (MPIF)‐1 were able to stimulate Gi/o‐coupled pathways, but MIP‐1δ, HCC‐1 and MPIF‐1 were unable to activate G14‐mediated stimulation of phospholipase Cβ activity. In addition, MIP‐1δ was unable to promote the phosphorylation of extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase. This suggests that different chemokines are able to selectively activate CCR1‐coupled pathways, probably because of differentintrinsic ligand efficacies. CCR1 and Gα14 or Gα16 are co‐expressed in several cell types and we hypothesize that selective activation of chemokine receptors provides a mechanism by which chemokines are able to fine‐tune intracellular signaling pathways.