Kil In Sup, Lee Jin Hyup, Yoon Soo Hyun, Bae Young Seuk, Kim Seontae, Shin Seoung Woo, Park Jeen-Woo
Redox Rep. 2015 Sep;20(5):228-33. doi: 10.1179/1351000215Y.0000000014. Epub 2015 May 27.
Leukocyte NADPH oxidase, which is active in neutrophils, is a membrane-bound enzyme that catalyzes the reduction of oxygen to O2(-) by using NADPH as an electron donor. Previously, we reported that casein kinase 2 (CK2), a ubiquitous and highly conserved Ser/Thr kinase, is responsible for p47(phox) phosphorylation and that phosphorylation of p47(phox) by CK2 regulates the deactivation of NADPH oxidase.
Here, we report that the residue Cys(196) of p47(phox) is a target of S-nitrosylation by S-nitrosothiol and peroxynitrite and that this modification enhanced phosphorylation of p47(phox) by CK2.
S-Nitrosylated p47(phox) enhanced CK2 b subunit binding, presumably due to alterations in protein conformation.
Taken together, we propose that S-nitrosylation of p47(phox) regulates the deactivation of NADPH oxidase via enhancement of p47(phox) phosphorylation by CK2.
白细胞NADPH氧化酶在中性粒细胞中具有活性,是一种膜结合酶,它利用NADPH作为电子供体催化氧气还原为超氧阴离子(O2(-))。此前,我们报道酪蛋白激酶2(CK2),一种普遍存在且高度保守的丝氨酸/苏氨酸激酶,负责p47(phox)的磷酸化,并且CK2对p47(phox)的磷酸化调节NADPH氧化酶的失活。
在此,我们报道p47(phox)的半胱氨酸残基Cys(196)是亚硝基硫醇和过氧亚硝酸盐进行S-亚硝基化修饰的靶点,并且这种修饰增强了CK2对p47(phox)的磷酸化作用。
S-亚硝基化的p47(phox)增强了CK2 β亚基的结合,推测这是由于蛋白质构象的改变。
综上所述,我们提出p47(phox)的S-亚硝基化通过增强CK2对p47(phox)的磷酸化来调节NADPH氧化酶的失活。