PHOSPHO-SPECIFIC ANTIBODIES TO PI3K REGULATORY SUBUNIT AND USES THEREOF
    9.
    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

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

    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。