Monocyte Chemotactic Protein-1 Receptor CCR2B Is a Glycoprotein That Has Tyrosine Sulfation in a Conserved Extracellular N-Terminal Region

摘要: Monocyte chemotactic protein-1 (MCP-1) binding to its receptor, CCR2B, plays an important role in a variety of diseases involving infection, inflammation, and/or injury. In our effort understand the molecular basis this interaction and biological consequences, we recognized conserved hexad amino acids at N-terminal extracellular domain several chemokine receptors, including CCR2B. Human embryonic kidney 293 cells expressing Flag-tagged CCR2B containing site-directed mutations region, 21-26, consensus tyrosine sulfation site were used determine MCP-1 consequences. The results showed that these are for consequent lamellipodium formation, chemotaxis, signal transduction adenylate cyclase inhibition Ca(2+) influx into cytoplasm. Mutations prevented did not significantly inhibit formation suggesting signaling events involved chemotaxis. was found be sulfated Tyr(26); abolished by substitution Tyr with Ala severely reduced Asp(25), part site. expressed N:-glycosylated, as N:-glycosidase F treatment receptor or growth tunicamycin size same level, from 50 45 kDa. Thus, is first member CC family shown glycoprotein Tyr. These post-translational modifications probably have significant functions.