MOLECULAR ACTIVATION OF NK CELLS THROUGH NKR-P1

描述（改编自申请人摘要）：研究 在本申请中提出的设计是为了检验假设， NKR-P1蛋白是识别和裂解特异性 肿瘤靶点此外，NKR-P1蛋白质的机制 产生用于NK细胞活化的跨膜信号将是 测定 具体目标是：（1）试图重建 NKR-P1突变细胞的裂解缺陷（其在裂解中有缺陷 一些，但不是所有的肿瘤靶点）， 编码单独的NKR-P1蛋白，从而定义靶点 每种蛋白质的库和这些蛋白质的需求， NK细胞活化。2)检查NK细胞是否存在 由不同NKR-P1蛋白组成的异二聚体，并评估 异源二聚体在NK细胞功能中的功能意义。3)到 表征酪氨酸激酶和两种酪氨酸磷酸化蛋白质 与NK细胞中的NKR-P1相关，并寻找额外的 淋巴细胞活化分子，可能在功能上与 与NK细胞中的NKR-P1结合。 4)为了研究建筑的结构主题， 信号转导所需的NKR-P1分子。 具体地涉及 利用聚合酶链反应诱导定点突变 在NKR-PI cDNA中。 在转染到我们的NKR-PI- RNK- 16中之后， 突变体，这些改变的分子的信号转导谱 将被确定。

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.