Protein kinase-dependent phosphorylation of the Menkes copper P-type ATPase
Protein kinase-dependent phosphorylation of the Menkes copper P-type ATPase
复制标题
DOI：
10.1016/s0006-291x(03)00329-2
复制
发表时间：
2003-03-28
影响因子：
3.1
通讯作者：
Camakaris, J
中科院分区：
文献类型：
--
作者：
Voskoboinik, I;Fernando, R;Camakaris, J
Menkes铜转运p型atp酶（ATP7A； MNK）是人体铜稳态的关键调节因子。它在向反式高尔基网络（TGN）中必需的铜原酶供应铜和从细胞中排出铜方面具有双重作用。这些功能是通过铜调控的MNK在TGN和质膜之间的运输来实现的。然而，调控NINK定位和生化功能的确切机制尚不清楚。在这里，我们通过一种假定的蛋白激酶研究了NINK的铜依赖性磷酸化。我们发现，在铜含量升高的情况下，野生型NINK在体内的磷酸化水平显著增加。铜依赖性磷酸化主要发生在两种磷酸肽的丝氨酸残基上。相比之下，细胞质铜结合位点发生突变的非运输型NINK突变体的磷酸化没有上调。我们的研究结果表明，激酶依赖性磷酸化在调节NINK蛋白的功能中具有潜在的重要作用。(C) 2003 Elsevier Science（美国）版权所有。
The Menkes copper-translocating P-type ATPase (ATP7A; MNK) is a key regulator of copper homeostasis in humans. It has a dual role in supplying copper to essential cuproenzymes in the trans-Golgi network (TGN) and effluxing copper from the cell. These functions are achieved through copper-regulated trafficking of MNK between the TGN and the plasma membrane. However, the exact mechanism(s) which regulate the localisation and biochemical functions of NINK are still unknown. Here we investigated copper-dependent phosphorylation of NINK by a putative protein kinase(s). We found that in the presence of elevated copper there was a substantial increase in phosphorylation of the wild-type NINK in vivo. The majority of copper-dependent phosphorylation was on serine residues in two phosphopeptides. In contrast, there was no up-regulation of phosphorylation of a non-trafficking NINK mutant with mutated cytosolic copper-binding sites. Our findings suggest a potentially important role of kinase-dependent phosphorylation in the regulation of function of the NINK protein. (C) 2003 Elsevier Science (USA). All rights reserved.