|Budget Amount *help
¥13,000,000 (Direct Cost : ¥13,000,000)
Fiscal Year 1998 : ¥3,800,000 (Direct Cost : ¥3,800,000)
Fiscal Year 1997 : ¥9,200,000 (Direct Cost : ¥9,200,000)
RP1O5 is a LRR molecule that is expressed on murine B lymphocytes. Its cross-linking with a monoclonal antibody delivers an activation signal that leads to resistance against apoptosis and massive proliferation in B cells. The following results were obtained in this term.
1. Molecular cloning of MD-1, a molecule which is associated with RP1O5. A molecule that is coprecipitated with RP1O5 was purified with the anti-RP1O5 antibody and amino acid sequence was determined. With the sequence, a cDNA clone was isolated. The molecule MD-1 is a secretory molecule but binds to the extracellular LRR of RP1O5.
2. The signaling pathways RP1O5 employs were examined using mice lacking signaling molecules. B cells lacking lyn, btk, Erk-specific MAP kinase, protein kinase C betaI/II, c-rel, nfkb1(p105) did not respond to the anti-RP1O5 antibody, indicating the presence of multiple signaling pathways downstream of RP1O5. There results were obtained by collaboration with Drs. S.Gerondakis (Australia) and A.Tarakhovsky (Germany).
3. A monoclonal antibody against human RPIO5 was established. Human RP1O5 was expressed on B lymphocytes, associated with human MD-1, and transmits an activation signal.
4. Mice lacking RP1O5 were established and now under investigation.