Kennelly Peter J
Department of Biochemistry - 0308, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Biochem J. 2003 Mar 1;370(Pt 2):373-89. doi: 10.1042/BJ20021547.
Protein phosphorylation/dephosphorylation has long been considered a recent addition to Nature's regulatory arsenal. Early studies indicated that this molecular regulatory mechanism existed only in higher eukaryotes, suggesting that protein phosphorylation/dephosphorylation had emerged to meet the particular signal-transduction requirements of multicellular organisms. Although it has since become apparent that simple eukaryotes and even bacteria are sites of protein phosphorylation/dephosphorylation, the perception widely persists that this molecular regulatory mechanism emerged late in evolution, i.e. after the divergence of the contemporary phylogenetic domains. Only highly developed cells, it was reasoned, could afford the high 'overhead' costs inherent in the acquisition of dedicated protein kinases and protein phosphatases. The advent of genome sequencing has provided an opportunity to exploit Nature's phylogenetic diversity as a vehicle for critically examining this hypothesis. In tracing the origins and evolution of protein phosphorylation/dephosphorylation, the members of the Archaea, the so-called 'third domain of life', will play a critical role. Whereas several studies have demonstrated that archaeal proteins are subject to modification by covalent phosphorylation, relatively little is known concerning the identities of the proteins affected, the impact on their functional properties, or the enzymes that catalyse these events. However, examination of several archaeal genomes has revealed the widespread presence of several ostensibly 'eukaryotic' and 'bacterial' protein kinase and protein phosphatase paradigms. Similar findings of 'phylogenetic trespass' in members of the Eucarya (eukaryotes) and the Bacteria suggest that this versatile molecular regulatory mechanism emerged at an unexpectedly early point in development of 'life as we know it'.
蛋白质磷酸化/去磷酸化长期以来一直被认为是自然界调控手段中的新成员。早期研究表明,这种分子调控机制仅存在于高等真核生物中,这表明蛋白质磷酸化/去磷酸化的出现是为了满足多细胞生物特定的信号转导需求。尽管后来已经很明显,简单的真核生物甚至细菌也是蛋白质磷酸化/去磷酸化的场所,但一种普遍的观念仍然存在,即这种分子调控机制在进化后期才出现,也就是在当代系统发育域分化之后。有人认为,只有高度发达的细胞才能承担获取专用蛋白激酶和蛋白磷酸酶所固有的高昂“管理”成本。基因组测序的出现为利用自然界的系统发育多样性作为严格检验这一假设的工具提供了机会。在追溯蛋白质磷酸化/去磷酸化的起源和进化过程中,古菌(所谓的“生命的第三域”)的成员将发挥关键作用。虽然几项研究已经证明古菌蛋白会受到共价磷酸化的修饰,但对于受影响蛋白的身份、对其功能特性的影响以及催化这些事件的酶却知之甚少。然而,对几个古菌基因组的研究揭示了几种表面上“真核”和“细菌”的蛋白激酶和蛋白磷酸酶模式的广泛存在。在真核生物和细菌成员中类似的“系统发育侵入”发现表明,这种多功能的分子调控机制在“我们所知的生命”发展过程中出人意料地早期就出现了。