McKay, PF and Imami, N and Johns, M and Taylor-Fishwick, DA and Sedibane, LM and Totty, NF and Hsuan, JJ and Palmer, DB and George, AJT and Foxwell, BMJ and Ritter, MA (1998) The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family. EUR J IMMUNOL , 28 (12) 4071 - 4083.
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The human gp200-MR6 molecule has previously been shown to have either an antagonistic or agonistic effect on IL-4 function, demonstrated by inhibition of IL-4-induced proliferation of T cells or mimicking of IL-4-induced maturation of epithelium, respectively. We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes. Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules. it comprises 1722 amino acids in tote (mature protein, 1695 amino acids; signal sequence, 27 amino acids) organized into 12 external domains (an N-terminal cysteine-rich domain, a fibronectin type II domain and 10 C-type carbohydrate recognition domains), a transmembrane region and a small cytoplasmic C terminus (31 amino acids) containing a single tyrosine residue (Y1679), but no obvious kinase domain. Strong amino acid sequence identity (77 %) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role. We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure.
|Title:||The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family|
|Keywords:||macrophage mannose receptor, B cell, thymus, IL-4, thymic microenvironment, SECRETORY PHOSPHOLIPASES A(2), MONOCLONAL-ANTIBODY NLDC-145, CARBOHYDRATE-RECOGNITION DOMAINS, INTERLEUKIN-4 RECEPTOR, DENDRITIC CELLS, TISSUE DISTRIBUTION, 180-KDA RECEPTOR, DEC-205 PROTEIN, DOWN-REGULATION, MAB MR6|
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