公开(公告)号：US08383799B2

公开(公告)日：2013-02-26

申请号：US12218834

申请日：2008-07-18

申请人： Ailan Guo ,  Anthony Possemato

发明人： Ailan Guo ,  Anthony Possemato

IPC分类号： C07H21/04 ,  C12Q1/68 ,  G01N33/53 ,  C12P21/02 ,  C12N15/09 ,  C12N5/10 ,  C12N1/21 ,  A61P35/00 ,  C12N1/15 ,  C12N15/63 ,  C07K14/47 ,  C07K16/18 ,  A61K31/713

CPC分类号： C12N15/1137 ,  C07K14/47 ,  C07K14/82 ,  C07K2319/00 ,  C12N9/1205 ,  C12N2310/14 ,  C12Q1/6841 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57423 ,  G01N33/57484

摘要： In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

摘要翻译： 根据本发明，在人非小细胞肺癌（NSCLC）中的新型基因易位（4p15,6q22），其导致结合部分钠依赖性磷酸转运蛋白同种型NaPi-3b蛋白（SLC34A2）的融合蛋白， 与原癌基因酪氨酸蛋白激酶ROS前体（ROS）激酶现已被鉴定。 预期SLC34A2-ROS融合蛋白将驱动NSCLC肿瘤亚组的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变型ROS激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的新融合蛋白的鉴定使得能够确定生物样品中这些突变型ROS激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变体多核苷酸为特征的癌症进展的方法 或多肽，其也由本发明提供。

公开(公告)号：US20100143918A1

公开(公告)日：2010-06-10

申请号：US12581126

申请日：2009-10-17

申请人： Ailan Guo ,  Ting-Lei Gu ,  Anthony Possemato

发明人： Ailan Guo ,  Ting-Lei Gu ,  Anthony Possemato

IPC分类号： C12Q1/68 ,  C07H21/00 ,  C12N15/74 ,  C12N5/07 ,  C07K14/00 ,  C07K16/00 ,  G01N33/53 ,  G01N33/574

CPC分类号： C07K14/82 ,  C07K14/47 ,  C07K2319/00 ,  C12N9/1205 ,  C12Q1/6841 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57423

摘要： In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion proteins are anticipated to drive the proliferation and survival of cancer cells, and particularly drive the proliferation and survival of a subgroup of NSCLC tumor cells. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

摘要翻译： 根据本发明，在人非小细胞肺癌（NSCLC）中的新型基因易位（4p15,6q22），其导致将部分钠依赖性磷酸转运蛋白同种型NaPi-3b蛋白（SLC34A2）与 原癌基因酪氨酸蛋白激酶ROS前体（ROS）激酶现已被鉴定。 预期SLC34A2-ROS融合蛋白将驱动癌细胞的增殖和存活，特别是促进NSCLC肿瘤细胞亚群的增殖和存活。 因此，本发明部分地提供分离的多核苷酸和编码所公开的突变型ROS激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。 所公开的新融合蛋白的鉴定使得能够确定生物样品中这些突变型ROS激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制以突变体多核苷酸为特征的癌症进展的方法 或多肽，其也由本发明提供。

公开(公告)号：US06495737B1

公开(公告)日：2002-12-17

申请号：US08909125

申请日：1997-08-11

申请人： Daniel F. Klessig ,  Ailan Guo

发明人： Daniel F. Klessig ,  Ailan Guo

IPC分类号： C12N1582

CPC分类号： C12N15/8279 ,  C12N9/14

摘要： The present invention provides methods and materials that enhance a plant's resistance to certain pathogens. A novel pathway is described and has been designated with the acronym, SI-SAR pathway, for salicylic acid-independent systemic acquired resistance. DNA constructs and methodologies are provided that facilitate the identification of compounds that activate this pathway. Methods are provided to enable the identification of novel genes and signaling components that are expressed when the SI-SAR pathway is activated. Transgenic plants with altered expression of these novel genes or signaling components of the pathway are expected to have enhanced resistance to plant pathogens. Also provided is a novel, pathogen-induced epoxide hydrolase that is inducible in the absence of SA.

摘要翻译： 本发明提供增强植物对某些病原体的抗性的方法和材料。 描述了一条新途径，并且已经用缩写SI-SAR途径指定了水杨酸独立系统获得性抗性。 提供DNA构建体和方法，其有助于鉴定激活该途径的化合物。 提供了方法来确定当SI-SAR途径被激活时表达的新基因和信号传导成分。 预期这些新基因或该途径的信号成分表达改变的转基因植物对植物病原体具有增强的抗性。 还提供了一种新型的病原体诱导的环氧化物水解酶，其在不存在SA时可诱导。