Ray William K, Potters Mark B, Haile January D, Kennelly Peter J
Department of Biochemistry, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USA.
Department of Chemistry, Centre College, Danville, KY 40422, USA.
Proteomes. 2015 May 15;3(2):89-116. doi: 10.3390/proteomes3020089.
The eukaryotic protein kinase (ePK) paradigm provides integral components for signal transduction cascades throughout nature However, while so-called typical ePKs permeate the and atypical ePKs dominate the kinomes of the . Intriguingly, the catalytic domains of the handful of deduced typical ePKs from the archaeon P2 exhibit significant resemblance to the protein kinases that phosphorylate translation initiation factor 2α (eIF2α) in response to cellular stresses. We cloned and expressed one of these archaeal eIF2α protein kinases, SsoPK4. SsoPK4 exhibited protein-serine/threonine kinase activity toward several proteins, including the homolog of eIF2α, aIF2α. The activity of SsoPK4 was inhibited by 3',5'-cyclic AMP (K of ~23 µM) and was activated by oxidized Coenzyme A, an indicator of oxidative stress in the Activation enhanced the apparent affinity for protein substrates, K, but had little effect on V. Autophosphorylation activated SsoPK4 and rendered it insensitive to oxidized Coenzyme A.
真核蛋白激酶（ePK）模式为自然界中的信号转导级联反应提供了不可或缺的组成部分。然而，虽然所谓的典型ePKs遍布[具体生物类别1]，但非典型ePKs在[具体生物类别2]的激酶组中占主导地位。有趣的是，从古菌P2中推导出来的少数典型ePKs的催化结构域与在细胞应激反应中磷酸化翻译起始因子2α（eIF2α）的蛋白激酶有显著相似之处。我们克隆并表达了其中一种古菌eIF2α蛋白激酶SsoPK4。SsoPK4对包括eIF2α的同源物aIF2α在内的几种蛋白质表现出蛋白丝氨酸/苏氨酸激酶活性。SsoPK4的活性受到3',5'-环磷酸腺苷（K约为23μM）的抑制，并被氧化型辅酶A激活，氧化型辅酶A是[具体生物类别3]中氧化应激的一个指标。激活增强了对蛋白质底物的表观亲和力K，但对V影响不大。自身磷酸化激活了SsoPK4并使其对氧化型辅酶A不敏感。
