Decoy receptor

Galliera E, Jala VR, Trent JO, et al. beta-Arrestin-dependent constitutive internalization of the human chemokine decoy receptor D6. J Biol Chem 2004 279(24) 25590-25597. 

Comerford I, Nibbs RJ. Post-translational control of chemokines a role for decoy receptors Immunol Lett 2005 96(2) 163-174. 

Macdonald TT. Decoy receptor springs to life and eases fibrosis. Nat Med 2006 12(1) 13-14. 

Martinez dlT, Locati M, Buracchi C, et al. Increased inflammation in mice deficient for the chemokine decoy receptor D6. Eur J Immunol 2005 35 1342-1346. 

The osteoprotegerin (OPG), also known as OCIF, TR1, or FDCR-1, is the first soluble protein that belongs to the TNF superfamily (Simonet et al. 1997 Kwon et al. 1998 Yun et al. 1998). Unlike RANK and RANKL, OPG is expressed in high concentrations in a variety of tissues and cellular types such as skin, bones, large arteries, and the gastrointestinal tract (Simonet et al. 1997). In bone, OPG is produced by stromal/OB cells (Hofbauer et al. 1999) and works as a decoy receptor for RANKL, competing with RANK for binding RANKL. Therefore, OPG is a potent inhibitor of the OCS. In vitro, OPG inhibits the differentiation and survival of osteoclast precursors, blocks their activation, and induces their apoptosis (Lacey et al. 1998 Yasuda et al. 1998 Hofbauer et al. 

Fig. 8. Schematic representation of aberrant mFas, which is expected to attenuate the Fas-mediated signaling. Aberrant mFas is functionally and structurally classified into main three types (a) the membrane-binding decoy receptor, (b) the membrane-binding decorative receptor, and (c) the membrane-unstable or soluble receptor. Although both mFas in models (a) and (b) are normally fixed on the membrane, the mFas in the former can bind Fas ligand, but is defective for trimerization, whereas the mFas in the latter would have no ability to bind Fas ligand in vivo because of conformational alteration. Like model (a), the mFas in model (c) can be reactive for Fas ligand, but it cannot transduce the apoptotic signal into the cytoplasmic death cascade because of incomplete trimerization due to an abnormal TM domain or truncation of the 1C domain. The hatched and jagged markings indicate deduced alterations of amino acid sequence or three-dimensional structure, respectively.

Thus, the KOB cells have been demonstrated ex vivo to prevent apoptosis by expression on their surfaces of function-ablating Fas antigen, which lacks the entire death domain. These aberrant Fas molecules probably behave as decoy receptors and interfere with the trimerization of normal Fas in a dominant negative manner, resulting in the impairment of signal transduction. 

Jenkins, M., Keir, M., and McCune, J. M., A membrane-bound Fas decoy receptor expressed by human thymocytes. J. Biol. CherrL 275, 7988—7993 (2000). 

Colotta F, Dower SK, Sims JE, Mantovani A. 1994. The type II decoy receptor A novel regulatory pathway for interleukin-1. Immunol Today. 15 562-566. 

Decoy receptors divertthe ligand and prevent apoptosis... 

Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr. Opin. Cell Biol. 1999 11 255-260. 

The type II receptor has a small cytoplasmic domain and cannot transduce signals. The extracellular domain of IL-IRII is released in soluble form at sites of local inflammation and into the serum during times of systemic inflammation. This soluble IL-IRII is produced in relatively large amounts, binds IL-ip much more strongly than it binds IL-la or IL-IRA, and functions as an endogenous inhibitor of IL-1 p. Both soluble and cell-associated forms of IL-IRII have therefore been called IL-1 decoy receptors. 

Recently, two products of the osteoblast have been identified that appear to be the final common pathway in coordinating osteoblast and osteoclast activity. The first, receptor activator of nuclear factor-KB (RANK) ligand, binds to a receptor on osteoclast progenitor cells and increases osteoclast differentiation and activity. The second, osteo-protegerin (OPG), serves as a decoy receptor for RANK ligand. When OPG binds to RANK ligand, the osteoclast-stimulation activity is prevented. The relative ratios of these two molecules determine bone turnover. 

Bone resorption is a physiological process prevented by the osteoblast secreting osteoclast inhibition factor (OCIF), more commonly called osteoprotegerin (OPG). OCIF is a nonmembrane-bound decoy receptor that resembles ODAR and prevents ODF from binding to ODAR and therefore causing preosteoclasts to remain undifferentiated (Fig. 10.5). Bone resorption is related to the body s response to injury or infection, a complex series of events called inflammation. 

Fig. 10.5 Osteoclast differentiation factors. Osteoblasts make monocyte colony stimulating factor (mCSF) that induces bone adherent monocytes carrying the corresponding receptor (mCSF Receptor) to fuse into osteoclast precursors (preosteoclasts). Preosteoclasts develop within the periosteum and are detectable by their expression of the osteoclast differentiation and activation receptor (ODAR). Osteoblasts also make cell-membrane bound and soluble osteoclast differentiation factors (ODF and sODF) that react with ODAR to cause preosteoclast differentiation. Finally, osteoblasts make osteoclast inhibition factor (OCIF), also called osteoprotegerin, which acts as an ODF decoy receptor and prevents ODF or sODF reacting with ODAR. ODAR is commonly referred to as RANK and ODF as the RANK ligand (RANKL) in the literature (see text)...

When the ODF/ODAR complex activates c-src to form a ruffled membrane, it also activates NFkB to activate the transcription factors that induce cathepsin K and acid phosphatase expression. Because ODF binds to ODAR/RANK, it is also known as the RANK ligand (RANKL). OCIF (OPG), the ODF decoy receptor, is RANK without its transmembrane and cytosolic domains. Thus OCIF = OPG and OPG ligand (OPGL) = RANKL = ODF. ODF, ODAR, and OCIF are related to TNFa or its receptor, TNFa family molecules (Table 10.1). 

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