微管亲和调节激酶2(MARK2)是一种Ser/Thr蛋白激酶,可调节细胞极性和免疫反应。这里,我们报告Orf9b,SARS-CoV-2基因组中编码的辅助蛋白之一,通过与自抑制性KAI结构域的相互作用增加MARK2活性。我们发现Orf9b的共表达增强了HEK293细胞中MARK2的激酶活性。Orf9b不结合缺乏KA1结构域的突变形式的MARK2或增强其活性。Orf9b在T595降低MARK2的抑制性磷酸化,而突变实验表明该位点对于Orf9b介导的MARK2活性的增强是不必要的。我们的结果表明,Orf9b通过结合自身抑制KA1结构域增强MARK2活性,与激酶结构域紧密相互作用。
Microtubule affinity-regulating kinase 2 (MARK2) is a Ser/Thr protein kinase that regulates cell polarity and immune responses. Here, we report that Orf9b, one of the accessory proteins encoded in the SARS-CoV-2 genome, increases MARK2 activity via interaction with the autoinhibitory KAI domain. We found that co-expression of Orf9b enhances the kinase activity of MARK2 in HEK293 cells. Orf9b does not bind to or enhance the activity of the mutant form of MARK2 lacking the KA1 domain. Orf9b lowers inhibitory phosphorylation of MARK2 at T595 while mutation experiments indicate that this site is dispensable for Orf9b-mediated enhancement of MARK2 activity. Our results suggest that Orf9b enhances MARK2 activity by binding the autoinhibitory KA1 domain, which closely interacts with the kinase domain.