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Dave, RK, Hume, DA, Elsegood, C and Kellie, S (2009) CD148/DEP-1 association with areas of cytoskeletal organisation in macrophages. Exp. Cell Res. 315:1734-44
In macrophages, tyrosine phosphorylation regulates many signalling pathways leading to growth, differentiation, activation, phagocytosis and adhesion. Protein tyrosine phosphatases (PTPs) represent a biochemical counterbalance to the activity of protein tyrosine kinases, thus regulating the dynamic phosphorylation state of a cell. CD148 is a receptor PTP that is highly expressed in macrophages and is further regulated by pro-inflammatory stimuli. CD148 is normally localised to the plasma membrane of macrophages. Following stimulation with CSF-1 or LPS, there was a re-distribution and concentration of CD148 in areas of membrane ruffling. Treatment of macrophages with anti-CD148 monoclonal antibody inhibited CSF-1-induced macrophage spreading, cytoskeletal re-arrangements and chemotaxis, without affecting cell survival. There were no detectable effects on the CSF-1 receptor-akt signalling pathway. These results are consistent with the hypothesis that CD148 is a regulator of macrophage activity.
Actins/metabolism; Animals; Antibodies, Monoclonal/pharmacology; Cell Proliferation/drug effects; Cell Surface Extensions/drug effects; Cell Surface Extensions/enzymology; Cell Survival/drug effects; Cells, Cultured; Chemotaxis/drug effects; Cross-Linking Reagents/pharmacology; Cytoskeleton/drug effects; Cytoskeleton/enzymology; Endocytosis/drug effects; Humans; Lipopolysaccharides/pharmacology; Macrophage Colony-Stimulating Factor/pharmacology; Macrophages/cytology; Macrophages/drug effects; Macrophages/enzymology; Mice; Mice, Inbred C57BL; Phosphorylation/drug effects; Protein Binding/drug effects; Protein Transport/drug effects; Receptor, Macrophage Colony-Stimulating Factor/metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism