Salvi Mauro, Sarno Stefania, Cesaro Luca, Nakamura Hideji, Pinna Lorenzo A
Department of Biological Chemistry, University of Padova, V.le G. Colombo 3, 35131 Padova, Italy.
Biochim Biophys Acta. 2009 May;1793(5):847-59. doi: 10.1016/j.bbamcr.2009.01.013. Epub 2009 Jan 31.
A weblogo has been generated from the sequences surrounding 433 Ser/Thr protein residues whose phosphorylation by protein kinase CK2 had been previously validated ("bona fide" CK2 phosphosites). This has been compared to the weblogo extracted from 2275 putative CK2 phosphosites displaying the motif pS/pT-x1-x2-D/E/pS (where x1 not=P) present in the human phosphoElm database including 10899 naturally occurring phosphosites. The two weblogos are strikingly similar supporting the notion that indeed the 2275 putative sites (accounting for 20.9% of the whole phosphoproteome they belong to), or at least the great majority of these are generated by CK2. This conclusion has been corroborated by the random validation of 8 of such putative CK2 sites (belonging to 5 different proteins) as real targets of CK2 in vitro and/or in cells, leading to the inclusion into the repertoire of bona fide CK2 targets of 5 new entries, namely: oxidative stress-responsive kinase-1, anthrax toxin receptor 1, hepatoma derived growth factor, EpsinR and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like.
基于433个丝氨酸/苏氨酸蛋白残基周围的序列生成了一个序列标志图，这些残基的蛋白激酶CK2磷酸化先前已得到验证（“真正的”CK2磷酸化位点）。已将此序列标志图与从2275个推定的CK2磷酸化位点中提取的序列标志图进行比较，这些位点在人类磷酸化蛋白质组数据库中显示出基序pS/pT-x1-x2-D/E/pS（其中x1≠P），该数据库包含10899个天然存在的磷酸化位点。这两个序列标志图惊人地相似，支持了这样一种观点，即确实这2275个推定位点（占它们所属的整个磷酸化蛋白质组的20.9%），或者至少其中绝大多数是由CK2产生的。通过对8个这样的推定CK2位点（属于5种不同蛋白质）作为CK2在体外和/或细胞中的真实靶点进行随机验证，这一结论得到了证实，从而将5个新条目纳入真正的CK2靶点库，即：氧化应激反应激酶-1、炭疽毒素受体1、肝癌衍生生长因子、EpsinR和BCL2/腺病毒E1B 19 kDa蛋白相互作用蛋白3样蛋白。
