|Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2003: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥4,800,000 (Direct Cost: ¥4,800,000)
We searched for secreted and membrane proteins from cultured bone marrow-derived mouse mast cells using retrovirus-mediated signal sequence trap method SST-REX. From this screening, we identified a novel membrane protein harboring a homology with inhibitory NK receptors. This protein harbors a single immunoglobulin like domain in the extracellular domein and three or four ITIM inhibitory motifs in the intracellular domain, and was designated as LMIRl that stands for Jeukocyte-associated mono Ig receptor-l. From the data base search, we also identified LMIR-2-6 that resemble LMIR1, and isolated full-length cDNAs for these proteins. LMIRl and 3 harbors ITIM motifs in the intracellular domain, and upon ligation, they induced phosphorylation of phosphatases SHP1, SHP2, and SHIP, thereby inducing inhibitory signals. On the other hand, LMIR2, 4, 5, and 6 have short intracellular domain, and associate with activating receptors including DAP10, DAP12 and FcRg through the transmembrane domains. We have developed monoclonal antibodies against LMIR-1-6. To clarify the physiological roles of these molecules especially in the control of mast cell activation, we are now trying to identify the ligands for LMIR1 and 3, and to generate the knockout mice for LMIRI-3.