title: The role of the ribosomal protein S19 C-terminus in altering the chemotaxis of leucocytes by causing functional differences in the C5a receptor response.
abstract: Ribosomal protein S19 (RP S19) oligomers have been discovered as the first chemoattractant of migrating monocytes/macrophages to apoptotic cells via the C5a receptor (C5aR). In contrast to C5a, a fusion of the C-terminus (I(134)-H(145)) of RP S19 to C5a, the C5a/RP S19 chimera, substitutes for the RP S19 oligomers and is able to replicate C5aR antagonist-induced and agonist-induced dual effects on neutrophil and monocyte chemotactic responses, respectively. We recently discovered a gain of binding affinity when the I(134)-H(145) inhibited the activation of neutrophil C5aR-mediated chemotactic pathways. However, the opposing ligand-dependent chemotactic mechanisms are not fully understood. In this study, a loss of this additional binding affinity appeared to cause the monocyte C5aR to activate an alternative signalling pathway. The p38 mitogen activated-protein kinase (MAPK) pathway was linked to cell migration rather than a classical extracellular-regulated kinase 1/2 pathway commonly used by C5a. C5aR internalization was not involved in the alternative chemotactic pathway. We propose a model of activation involving a C5aR co-molecule that interferes with the C5aR-Gi protein interaction upon binding to the I(134)-H(145) in neutrophils; however, a free I(134)-H(145) from the C5aR co-molecule can guide the alternative activation of the chemotactic p38MAPK pathway in monocytes/macrophages.
authors: Department of Molecular Pathology, Faculty of Life Science, Kumamoto University Graduate School, Honjyo 1-1-1, 860-8556 Kumamoto, Japan.
authors: Hiroshi
authors: H
authors: Nishiura
authors: Rui
authors: R
authors: Zhao
authors: Tetsuro
authors: T
authors: Yamamoto