TRAIL interacts via a complex receptor system to preferentially induce apoptosis of tumor cells in vivo and in vitro (1). In human, two signaling receptors (TRAIL R1 and TRAIL R2) and three decoy receptors (TRAIL R3, TRAIL R4, and OPG) for TRAIL exist. Mouse homologues of human TRAIL R1, -3, and -4 have not been found. Three novel mouse genes (TNF RH1, -2, and -3) that encode proteins with the classic TNF receptor cysteine-rich domains (CRDs) have been identified. These mouse genes are closely clustered on distal mouse chromosome 7 and do not have orthologues in the corresponding human chromosomal region (2). TNF RH1 and -2 have been implicated as decoy receptors for mouse TRAIL and named mDcTRAIL R1/TNFRSF23 and mDcTRAIL R2/TNFRSF22, respectively. The ligand for TNF RH3 is not known (1).
The mouse decoy TRAIL R2 (mDcTRAIL R2) gene encodes a 198 amino acid (aa) residues type I transmembrane protein with a putative 39 aa signal peptide, a 136 aa extracellular domain, a 18 aa transmembrane region, and a 5 aa cytoplasmic tail (1, 2). An alternatively spliced variant encoding a secreted soluble receptor of 180 aa has also been described. The transmembrane and soluble receptors are known as mDcTRAIL R2L and mDcTRAIL R2S, respectively. Both mDcTRAIL R2 isoforms and the GPI-linked mDcTRAIL R1 bind TRAIL specifically but are incapable of triggering signal transduction. Mouse DcTRAIL R1 and mDcTRAIL R2 share 71% sequence identity (3). The two receptors have similar structural modules in their CRDs, which differ from those found in the CRDs of mTNF RH3 (2, 3). Mouse DcTRAIL R1 preferentially binds mTRAIL while mDcTRAIL R2 binds both human and mTRAIL. mRNA of mouse DcTRAIL R1 and -2 are expressed at low levels in many mouse tissues and at higher levels in several mouse cell lines.
