Dubois T, Kerai P, Zemlickova E, Howell S, Jackson T R, Venkateswarlu K, Cullen P J, Theibert A B, Larose L, Roach P J, Aitken A
University of Edinburgh, Division of Biomedical and Clinical Laboratory Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD.
J Biol Chem. 2001 Jun 1;276(22):18757-64. doi: 10.1074/jbc.M010005200. Epub 2001 Mar 2.
Mammalian casein kinases I (CKI) belong to a family of serine/threonine protein kinases involved in diverse cellular processes including cell cycle progression, membrane trafficking, circadian rhythms, and Wnt signaling. Here we show that CKIalpha co-purifies with centaurin-alpha(1) in brain and that they interact in vitro and form a complex in cells. In addition, we show that the association is direct and occurs through the kinase domain of CKI within a loop comprising residues 217-233. These residues are well conserved in all members of the CKI family, and we show that centaurin-alpha(1) associates in vitro with all mammalian CKI isoforms. To date, CKIalpha represents the first protein partner identified for centaurin-alpha(1). However, our data suggest that centaurin-alpha(1) is not a substrate for CKIalpha and has no effect on CKIalpha activity. Centaurin-alpha(1) has been identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein. Centaurin-alpha(1) contains a cysteine-rich domain that is shared by members of a newly identified family of ADP-ribosylation factor guanosine trisphosphatase-activating proteins. These proteins are involved in membrane trafficking and actin cytoskeleton rearrangement, thus supporting a role for CKIalpha in these biological events.
哺乳动物酪蛋白激酶I（CKI）属于丝氨酸/苏氨酸蛋白激酶家族，参与多种细胞过程，包括细胞周期进程、膜运输、昼夜节律和Wnt信号传导。在此我们表明，CKIα在脑中与centaurin-α(1) 共同纯化，并且它们在体外相互作用并在细胞中形成复合物。此外，我们表明这种结合是直接的，并且通过CKI的激酶结构域在包含217 - 233位残基的环内发生。这些残基在CKI家族的所有成员中都高度保守，并且我们表明centaurin-α(1) 在体外与所有哺乳动物CKI同工型相关联。迄今为止，CKIα是已鉴定出的centaurin-α(1) 的首个蛋白质伴侣。然而，我们的数据表明centaurin-α(1) 不是CKIα的底物，并且对CKIα活性没有影响。Centaurin-α(1) 已被鉴定为一种磷脂酰肌醇3,4,5-三磷酸结合蛋白。Centaurin-α(1) 包含一个富含半胱氨酸的结构域，该结构域为新鉴定的ADP-核糖基化因子鸟苷三磷酸酶激活蛋白家族成员所共有。这些蛋白质参与膜运输和肌动蛋白细胞骨架重排，因此支持CKIα在这些生物学事件中的作用。
