| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
4F2 antigen is expressed on the membrane of proliferating cells such as cancer cells and activated lymphocytes. Although it is a hetrodimer protein composed of heavy and light chains, the structure of its light chain is still unknown. According to the AAs sequencing analysis, the light chain had a homology to hnRNP A2/B1 (heterogeneous nuclear ribonucleoprotein A2/B1) proteins. The purpose of this study is to clarify the molecular structure and function of 4F2 antigen, especially of its light chin, and its pathological significance.
First, in order to identify the light chain, we constructed tagged cDNA of hnRNP A2 and B1 proteins, and transfected them in cultured cells, and demonstrated that only the hnRNP B1 protein was incorporated in the 4F2 antigen. We generated a monoclonal antibody specific to hnRNP B1. The analysis using the antibody indicated that 4F2 light chain was whether modified hnRNP B1 or its another isofrom. Further investigation revealed the followings ; 1) hnRNP B1 protein was post-transitionally modified, that is, phosphorylated, 2) its was expressed on the cell membrane of some kind of cells though it was mainly localized in the nucleus, 3) it was dissociated from the heavy chain under reduced condition. Its expression was cell-specifically regulated and its splcing-isoforms possibly exist in the skin and testis.
Because its was reported that the patient of auto-immune disease like SLE had antibodies against hnRNP A2/B1 proteins, we also examined the pahological significance of 4F2 light chain using model mice of autoimmune disease. Anti-hnRNP A2/B1 anitbodies possibly participate in the pathogenesis of renal lesion of Newzealand-B/W mice but not in MRL-lpr/lpr mice. We are carring forward the experiment to analyze it.
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