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    PHOSPHO-SPECIFIC ANTIBODIES TO PI3K REGULATORY SUBUNIT AND USES THEREOF
    7.
    发明申请
    PHOSPHO-SPECIFIC ANTIBODIES TO PI3K REGULATORY SUBUNIT AND USES THEREOF 审中-公开
    磷酸特异性抗PI3K调节子及其用途

    公开(公告)号：US20080014598A1

    公开(公告)日：2008-01-17

    申请号：US11744753

    申请日：2007-05-04

    申请人： Thorsten Wiederhold ,  Valerie Goss ,  Albrecht Moritz ,  Klarisa Rikova ,  Ting-Lei Gu ,  Peter Hornbeck

    发明人： Thorsten Wiederhold ,  Valerie Goss ,  Albrecht Moritz ,  Klarisa Rikova ,  Ting-Lei Gu ,  Peter Hornbeck

    IPC分类号： G01N33/573 ,  C07K16/18 ,  C12N5/06

    CPC分类号： C07K16/40 ,  C12Q1/485 ,  G01N33/6842 ,  G01N2333/91215

    摘要： The invention discloses ten newly discovered PI3K regulatory subunit phosphorylation sites, tyrosines 467, 452, 463, and 470 in PI3KR1 (PI3Kp85 alpha), tyrosines 464, 460, and 467 in PI3KR2 (PI3Kp85 beta), and tyrosines 199, 184, and 202 in PI3KR3 (PI3Kp55 gamma), and provides reagents, including polyclonal and monoclonal antibodies, that selectively bind to PI3K when phosphorylated at one of the disclosed sites. Also provided are assays utilizing this reagent, including methods for determining the phosphorylation of PI3K in a biological sample, selecting a patient suitable for PI3K inhibitor therapy, profiling PI3K activation in a test tissue, and identifying a compound that modulates phosphorylation of PI3K in a test tissue, by using a detectable reagent, such as the disclosed antibody, that binds to PI3K only when phosphorylated at a disclosed site. The sample or test tissue may be taken from a subject suspected of having cancer, such as lymphoma, glioma, and colon cancer, involving altered PI3K signaling.

    摘要翻译： 本发明公开了PI3KR1（PI3Kp85α），PI3KR2（PI3Kp85β）中酪氨酸464,460和467和酪氨酸199,184和202中的10个新发现的PI3K调节亚基磷酸化位点，酪氨酸467,452,463和470 在PI3KR3（PI3Kp55γ）中，并且提供试剂，包括多克隆和单克隆抗体，当在所公开的位点之一磷酸化时选择性地结合PI3K。 还提供了使用该试剂的测定法，包括用于测定生物样品中PI3K的磷酸化的方法，选择适合于PI3K抑制剂治疗的患者，在测试组织中分析PI3K活化，以及鉴定在测试中调节PI3K磷酸化的化合物 组织，通过使用仅在所公开的位点磷酸化时与PI3K结合的可检测试剂，例如所公开的抗体。 样品或测试组织可以取自怀疑患有癌症的受试者，例如淋巴瘤，神经胶质瘤和结肠癌，涉及改变的PI3K信号传导。

    Reagents for the detection of protein phosphorylation in signaling pathways
    10.
    发明授权
    Reagents for the detection of protein phosphorylation in signaling pathways 有权
    用于检测信号通路中蛋白质磷酸化的试剂

    公开(公告)号：US07999080B2

    公开(公告)日：2011-08-16

    申请号：US12309310

    申请日：2007-07-13

    申请人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

    发明人： Peter Hornbeck ,  Valerie Goss ,  Kimberly Lee ,  Ting-Lei Gu ,  Albrecht Moritz

    IPC分类号： C07K16/18

    CPC分类号： C12Q1/485 ,  C07K16/18 ,  C07K16/40 ,  C07K16/44 ,  G01N33/68 ,  G01N33/6842 ,  G01N33/6845 ,  G01N33/6848 ,  G01N33/6872

    摘要： The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, adhesion/extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding/repair/replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G/regulator proteins, inhibitor proteins, motor/contractile proteins, phosphatase, protease, Ser/Thr protein kinases, Protein kinase (Tyr)s, receptor/channel/cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

    摘要翻译： 本发明公开了在信号转导蛋白和途径中鉴定的新型磷酸化位点，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及使用 用于此目的的试剂。 鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，粘附/细胞外基质蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，伴侣蛋白，染色质，DNA结合/修复/复制蛋白， 细胞骨架蛋白，内质网或高尔基体蛋白，酶蛋白，G /调节蛋白，抑制蛋白，运动/收缩蛋白，磷酸酶，蛋白酶，Ser / Thr蛋白激酶，蛋白激酶（Tyr），受体/通道/细胞表面蛋白， RNA结合蛋白，转录调节物，肿瘤抑制蛋白，泛素偶联系统蛋白和功能未知的蛋白。