Vaid Ankush, Sharma Pushkar
Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
J Biol Chem. 2006 Sep 15;281(37):27126-33. doi: 10.1074/jbc.M601914200. Epub 2006 Jun 29.
Intracellular cell signaling cascades of protozoan parasite Plasmodium falciparum are not clearly understood. We have reported previously (Kumar, A., Vaid, A., Syin, C., and Sharma, P. (2004) J. Biol. Chem. 279, 24255-24264) the identification and characterization of a protein kinase B-like enzyme in P. falciparum (PfPKB). PfPKB lacks the phosphoinositide-interacting pleckstrin homology domain present in mammalian protein kinase B. Therefore, the mechanism of PfPKB regulation was expected to be different from that of the host and had remained unknown. We have identified calmodulin (CaM) as the regulator of PfPKB activity. A CaM binding domain was mapped in the N-terminal region of PfPKB. CaM, in a calcium-dependent manner, interacts with this domain and activates PfPKB. CaM associates with PfPKB in the parasite and regulates its activity. Furthermore phospholipase C acts as an upstream regulator of this cascade as it facilitates the release of calcium from intracellular stores. This is one of the first multicomponent signaling pathways to be dissected in the malaria parasite.
恶性疟原虫这种原生动物寄生虫的细胞内信号级联反应尚未完全清楚。我们之前曾报道过（库马尔，A.，瓦伊德，A.，西因，C.，以及夏尔马，P.（2004年）《生物化学杂志》279卷，24255 - 24264页）在恶性疟原虫中鉴定并表征了一种类蛋白激酶B酶（PfPKB）。PfPKB缺乏哺乳动物蛋白激酶B中存在的与磷酸肌醇相互作用的普列克底物蛋白同源结构域。因此，预计PfPKB的调节机制与宿主的不同，并且一直未知。我们已鉴定出钙调蛋白（CaM）作为PfPKB活性的调节因子。在PfPKB的N端区域定位了一个CaM结合结构域。CaM以钙依赖的方式与该结构域相互作用并激活PfPKB。CaM在寄生虫中与PfPKB结合并调节其活性。此外，磷脂酶C作为该级联反应的上游调节因子，因为它促进细胞内储存的钙的释放。这是在疟原虫中解析的首批多组分信号通路之一。
