Toll-like receptors stimulate regulated intramembrane proteolysis of the CSF-1 receptor through Erk activation.
The CSF-1 receptor is a protein-tyrosine kinase that regulates the renewal, differentiation and activation of monocytes and macrophages. We have recently shown that the CSF-1 receptor undergoes regulated intramembrane proteolysis, or RIPping. Here, we report that RIPping can be observed in response to pathogen-associated molecules, which act through Toll-like receptors (TLRs). TLR-induced CSF-1 receptor RIPping is largely independent of protein kinase C, while maximal RIPping depends on Erk activation. Our studies show that CSF-1 receptor RIPping can be activated by various intracellular signal transduction pathways and that RIPping is likely to play an important role during macrophage activation.
Glenn
Gary
G
Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-1030, USA.
van der Geer
Peter
P
D051722:ADAM Proteins / Q000037:antagonists & inhibitors; D000072198:ADAM17 Protein; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology* / Q000276:immunology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein