公开(公告)号：US20070036793A1

公开(公告)日：2007-02-15

申请号：US10565058

申请日：2004-07-16

申请人： David Hardie ,  Dario Alessi ,  Jerome Boudeau

发明人： David Hardie ,  Dario Alessi ,  Jerome Boudeau

IPC分类号： A61K39/395 ,  G01N33/53 ,  C12P21/06 ,  C12N9/12

CPC分类号： C12N9/1205 ,  C07K14/82

摘要： A method for identifying a compound for use in modulating, for example promoting, the activation or phosphorylation of AMPK (AMP-activated protein kinase) or AMPK subfamily member in a cell, the method comprising the steps of (1) determining whether a test compound modulates, for example promotes, the protein kinase activity of LKB1 and (2) selecting a compound which modulates, for example promotes, the protein kinase activity of LKB1. The protein kinase activity may be tested using AMPK or an AMPK subfamily member, or a peptide encompassing the T-loop region of AMPK or an AMPK subfamily member. The LKB1 may be in a preparation or complex with STRAD and/or M025, which has much greater kinase activity than LKB1 in the absence of these accessory proteins. The LKB1, STRAD or M025 may be recombinant. The AMPK subfamily member may be AMPKα1, AMPKα2, NUAK1, NUAK2, BRSK1, BRSK2, SIK, QIK, QSK, MARK1, MARK2, MARK3, MARK4 or MELK.

摘要翻译： 一种用于鉴定用于调节例如促进细胞中AMPK（AMP-活化蛋白激酶）或AMPK亚族成员的活化或磷酸化的化合物的方法，所述方法包括以下步骤：（1）确定测试化合物 调节，例如促进LKB1的蛋白激酶活性，和（2）选择调节，例如促进LKB1的蛋白激酶活性的化合物。 可以使用AMPK或AMPK亚族成员或包含AMPK的T环区域或AMPK亚族成员的肽来测试蛋白激酶活性。 LKB1可能与STRAD和/或M025的制备或复合物相比，在没有这些辅助蛋白质的情况下，其具有比LKB1大得多的激酶活性。 LKB1，STRAD或M025可以是重组的。 AMPK亚族成员可以是AMPKalpha1，AMPKalpha2，NUAK1，NUAK2，BRSK1，BRSK2，SIK，QIK，QSK，MARK1，MARK2，MARK3，MARK4或MELK。