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1. 发明申请

WO2005116267A2 EMISSION RATIOMETRIC INDICATORS OF PHOSPHORYLATION BY C-KINASE 审中-公开
标题翻译：通过C-激酶发射磷酸化的发射比率指标
公开(公告)号：WO2005116267A2
公开(公告)日：2005-12-08
申请号：PCT/US2005/018662
申请日：2005-05-26
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , VIOLIN, Jonathan, D. , NEWTON, Alexandra, C. , TSIEN, Roger, Y. , ZHANG, Jin
发明人： VIOLIN, Jonathan, D. , NEWTON, Alexandra, C. , TSIEN, Roger, Y. , ZHANG, Jin
IPC分类号： C12Q1/68
CPC分类号： C12N9/1205 , C07K14/43595 , C07K2319/00 , C07K2319/60 , C12Q1/37 , C12Q1/42 , C12Q1/485 , G01N33/542 , G01N2333/43595
摘要： A chimeric phosphorylation indicator (CPI) as provided herein can contain a donor molecule, a phosphorylatabe domain, a phosphoaminoacid binding domain (PAABD), and an acceptor molecule. Where the phosphorylatable domain is phosphorylatable by protein kinase C (PKC), the CPI is a c-kinase activity reporter (CKAR). Donor and acceptor molecules may be, independently, fluorescent proteins such as non-oligomerizing fluorescent proteins. A CPI can contain a phosphorylatable polypeptide and a fluorescent protein; the phosphorylatable polypeptide may be contained within the sequence of the fluorescent protein, or the fluorescent protein may be contained within the sequence of the phosphorylatable polypeptide. The spatiotemporal properties of the PKC signal pathway may be tested with CKAR, calcium-sensing fluorophores and FRET-based translocation assays. Polynucleotides encoding such CPIs, and kits containing the indicators and/or the polynucleotides, are provided. A method of using the chimeric phosphorylation indicators to detect a kinase or phosphatase in a sample is provided.
摘要翻译：本文提供的嵌合磷酸化指示剂（CPI）可以含有供体分子，磷酰胺结构域，磷酸氨基酸结合结构域（PAABD）和受体分子。当可磷酸化结构域由蛋白激酶C（PKC）磷酸化时，CPI是c-激酶活性报告物（CKAR）。供体和受体分子可以独立地是荧光蛋白，例如非低聚荧光蛋白。 CPI可以含有可磷酸化的多肽和荧光蛋白; 可磷酸化多肽可以包含在荧光蛋白的序列内，或者荧光蛋白可以包含在可磷酸化多肽的序列内。可以用CKAR，钙感应荧光团和基于FRET的易位测定来测试PKC信号通路的时空性质。提供了编码这种CPI的多核苷酸，以及含有指示剂和/或多核苷酸的试剂盒。提供了使用嵌合磷酸化指示剂来检测样品中的激酶或磷酸酶的方法。

2. 发明申请

WO2009151542A2 NICOTINIC ACID RECEPTOR LIGANDS 审中-公开
公开(公告)号：WO2009151542A2
公开(公告)日：2009-12-17
申请号：PCT/US2009/003218
申请日：2009-05-27
申请人： DUKE UNIVERSITY , LEFKOWITZ, Robert, J. , DEWIRE, Scott, M. , WHALEN, Erin, J. , VIOLIN, Jonathan, D. , WALTERS, Robert, W.
发明人： LEFKOWITZ, Robert, J. , DEWIRE, Scott, M. , WHALEN, Erin, J. , VIOLIN, Jonathan, D. , WALTERS, Robert, W.
IPC分类号： G01N33/68 , C07K14/705
CPC分类号： G01N33/566 , C07K14/705 , G01N2333/726 , G01N2800/044
摘要： The present invention relates, in general, to nicotinic acid receptor ligands and, in particular, to ligands that have a relative efficacy for activating a G- protein-coupled receptor function (e.g., signaling) that is greater than their relative efficacy for stimulating β-arrestin function (e.g., recruitment and/or signaling). The invention further relates to the use of such "biased ligands" to decrease triglycerides levels and to potentially increase high density lipoprotein (HDL) levels in patients and potentially lower low density lipoprotein (LDL) and/or very low density lipoprotein (VLDL) levels. In addition, the invention relates to methods of identifying such "biased ligands".
摘要翻译：本发明一般涉及烟酸受体配体，尤其涉及具有激活G-蛋白偶联受体功能（例如，信号传导）的相对功效的配体，其大于其刺激ß的相对功效 -arrestin功能（例如招聘和/或信令）。本发明还涉及这种“有偏配体”降低甘油三酯水平并潜在地增加患者中高密度脂蛋白（HDL）水平以及潜在地降低低密度脂蛋白（LDL）和/或极低密度脂蛋白（VLDL）水平的用途。此外，本发明涉及鉴定这种“有偏配体”的方法。

3. 发明申请

WO2008103393A1 PROTEIN TRAFFICKING 审中-公开
标题翻译：蛋白质运输
公开(公告)号：WO2008103393A1
公开(公告)日：2008-08-28
申请号：PCT/US2008/002257
申请日：2008-02-21
申请人： DUKE UNIVERSITY , LEFKOWITZ, Robert, J. , VIOLIN, Jonathan, D.
发明人： LEFKOWITZ, Robert, J. , VIOLIN, Jonathan, D.
IPC分类号： G01N33/53 , G01N33/567 , C12N5/00 , C12N5/02
CPC分类号： G01N33/6803 , G01N2333/726
摘要： The present invention relates, in general, to protein trafficking, and, in particular, to a method of measuring protein trafficking to and from a plasma membrane.
摘要翻译：本发明一般涉及蛋白质的运输，尤其涉及一种测定向质膜和从质膜传送蛋白质的方法。

4. 发明申请

WO2008021552A2 BIASED LIGANDS AND METHODS OF IDENTIFYING SAME 审中-公开
标题翻译：偏差配体和鉴定方法
公开(公告)号：WO2008021552A2
公开(公告)日：2008-02-21
申请号：PCT/US2007/018394
申请日：2007-08-20
申请人： DUKE UNIVERSITY , LEFKOWITZ, Robert, J. , RAJAGOPAL, Keshava , WHALEN, Erin, J. , DRAKE, Matthew, T. , VIOLIN, Jonathan, D. , ROCKMAN, Howard, A. , DEWIRE, Scott, M.
发明人： LEFKOWITZ, Robert, J. , RAJAGOPAL, Keshava , WHALEN, Erin, J. , DRAKE, Matthew, T. , VIOLIN, Jonathan, D. , ROCKMAN, Howard, A. , DEWIRE, Scott, M.
IPC分类号： G01N33/53
CPC分类号： G01N33/74 , G01N2333/726
摘要： The present invention relates to G protein-coupled receptor ligands having a relative efficacy for stimulating β-arrestin/G protein-coupled receptor kinase (GRK) function (e.g., signaling) that is greater than their relative efficacy for stimulating G-protein signaling function. These "β-arrestin/GRK biased ligands" can act as agonists or antagonists of G protein-mediated signaling and agonists of β-arrestin/GRK-mediated signal transduction. The invention further relates to methods of identifying such ligands and to methods of using same in a variety of therapeutic settings.
摘要翻译：本发明涉及具有刺激β-抑制蛋白/ G蛋白偶联受体激酶（GRK）功能（例如，信号传导）的相对功效的G蛋白偶联受体配体，其比它们的相对刺激G蛋白信号传导功能的功效。这些“β-arrestin / GRK偏爱配体” 可以充当G蛋白介导的信号传导的激动剂或拮抗剂和β-arrestin / GRK介导的信号转导的激动剂。本发明进一步涉及鉴定此类配体的方法和在各种治疗环境中使用它们的方法。

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