MOLECULAR ACTIVATION OF NK CELLS THROUGH NKR-P1

描述(改编自申请人的摘要)：研究 在本申请中提出的，旨在检验以下假设 NKR-P1蛋白是识别和裂解特定抗原所必需的 肿瘤靶点。此外，NKR-P1蛋白的作用机制 为NK细胞激活产生跨膜信号将是 下定决心。具体目标是：1)试图重组 NKR-P1突变细胞的裂解缺陷(裂解缺陷 一些，但不是所有的肿瘤靶点) 编码单个NKR-Pl蛋白，从而定义靶标 每种蛋白质的谱系和对这些蛋白质的要求 NK细胞活化。2)检查NK细胞是否存在 由不同NKR-P1蛋白组成的异源二聚体 异源二聚体在NK细胞功能中的功能意义。3)至 一种酪氨酸激酶和两种酪氨酸磷酸化蛋白的特性 与NK细胞中的NKR-P1相关，并寻找其他 可能在功能上相关的淋巴细胞激活分子 与NK细胞中的NKR-P1结合。4)考察《红楼梦》的结构主题 信号转导所需的NKR-Pl分子。具体地说， 利用聚合酶链式反应诱导定点突变 在NKR-PI的cDNA中。转染NKR-PI-RNK-16细胞后 突变体，这些改变的分子的信号转导轮廓 将会被确定。

DESCRIPTION (Adapted from the Applicant's Abstract): The studies proposed in this application are designed to test the hypothesis that NKR-P1 proteins are required for the recognition and lysis of specific tumor targets. In addition, the mechanisms by which NKR-P1 proteins generate transmembrane signals for NK cell activation will be determined. The specific aims are: 1) To attempt to reconstitute the lytic defects of NKR-P1 mutant cells (which is defective in the lysis of some, but not all, tumor targets) by transfecting them with the cDNAs encoding the individual NKR-Pl proteins, thus defining the target repertoire for each protein and the requirements for these proteins in NK cell activation. 2) To examine NK cells for the presence of heterodimers composed of different NKR-P1 proteins and to assess the functional significance of heterodimers in NK cell function. 3) To characterize a tyrosine kinase and two tyrosine phosphorylated proteins associated with NKR- P1 in NK cells, and to search for additional lymphocyte activation molecules which might be functionally associated with NKR-P1 in NK cells. 4) To examine the structural motifs of the NKR-Pl molecules required for signal transduction. Specifically, to utilize the polymerase chain reaction to induce site-directed mutations in the NKR-PI cDNA. Following transfection into our NKR-PI- RNK- 16 mutants, the signal transduction profiles of these altered molecules will be determined.