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Studies on signal transduction in generation and development of cancers.

癌症发生和发展中信号转导的研究。

基本信息

批准号：
10460037
负责人：
FUKUI Yasuhisa
金额：
$ 8.06万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Phosphatodylinosito1 3-kinase is the enzyme that produces PIPィイD23ィエD2 in vivo. PIP3ィイD2aィエD2 acts as an important second messenger to activate various downstream factors. However, despite the efforts of a number of laboratories, there are not enough downstream factors identified to explain variety of cell responses dependent of PI 3-kinase pathway. We have produced PIPィイD23ィエD2 analogue beads and used them for identification of PIPィイD23ィエD2 binding proteins, which are the candidates for the downstream factors of PIPィイD23ィエD2 PIP3BP is one of such PIPィイD23ィエD2 binding proteins which localizes in the nucleus. Since it is homologous to Arf-GAP, it is likely that this protein is involved in vesicle transport. This year, we established hybridoma lines which produce BP-kinesin, a binding protein for PIP3B. We also identified SWAP70 as a PIPィイD23ィエD2 binding protein which is suggested to be a subunit of a B-cell specific recombinase complex. SWAP70 localized in the cytoplasm but moved into nucleus when co-expressed with a constitutively active PI 3-kinase. This translocation was sensitive to wortmannin, PI 3-kinase inhibitor. SWAP70 was overexpressed in Sf9 cells and purified. In vitro analysis for nuclear translocation revealed that SWAP70 is impo1-ted to the nucleus in an ATP dependent manner. It is of interest to test the role of in this PIPィイD23ィエD2 System.

磷脂酰肌醇1 3-激酶是在体内产生PIP磷脂酰肌醇D23磷脂酰肌醇D2的酶。PIP 3受体D2 a受体D2作为一个重要的第二信使激活下游的各种因素。然而，尽管许多实验室的努力，有没有足够的下游因素确定，以解释依赖于PI 3-激酶途径的各种细胞反应。我们已经制备了PIP P23 β D2类似物珠，并将其用于鉴定PIP P23 β D2结合蛋白，其是PIP P23 β D2下游因子的候选物。PIP 3BP是定位于细胞核中的此类PIP P23 β D2结合蛋白之一。由于它是同源的Arf-GAP，这是可能的，这种蛋白质参与囊泡运输。今年，我们建立了产生BP-驱动蛋白的杂交瘤细胞系，BP-驱动蛋白是PIP 3B的结合蛋白。我们还鉴定了SWAP 70作为PIP P23蛋白D2结合蛋白，其被认为是B细胞特异性重组酶复合物的亚基。SWAP 70定位于细胞质中，但当与组成型活性PI 3-激酶共表达时移到细胞核中。该易位对PI 3-激酶抑制剂渥曼青霉素敏感。SWAP 70在Sf 9细胞中过表达并纯化。体外核转位分析表明SWAP 70以ATP依赖的方式进入细胞核。测试在该PIP双极D23双极D2系统中的作用是有意义的。