RRC ID 38561
Author Nishiura H, Zhao R, Yamamoto T.
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.
Journal J Biochem
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.
Volume 150(3)
Pages 271-7
Published 2011-9-1
DOI 10.1093/jb/mvr067
PII mvr067
PMID 21613290
MeSH Cell Line, Tumor Chemotactic Factors / metabolism Chemotaxis, Leukocyte* Complement C5a / chemistry Complement C5a / metabolism Humans Macrophages / physiology Mast Cells / cytology Mast Cells / metabolism Monocytes / physiology* Neutrophils / physiology Protein Binding Receptor, Anaphylatoxin C5a / metabolism* Ribosomal Proteins / genetics Ribosomal Proteins / metabolism* Signal Transduction p38 Mitogen-Activated Protein Kinases / chemistry p38 Mitogen-Activated Protein Kinases / metabolism
IF 2.476
Times Cited 11
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells