Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Sci Signal. 2012 May 8;5(223):pe20. doi: 10.1126/scisignal.2003085.
Many signal transduction pathways comprise protein kinase cascades in which the activity of each component is controlled by phosphorylation and dephosphorylation. A new layer of kinase regulation involving nucleotide binding has now been unraveled. Phosphorylation of Akt at two regulatory sites plays a major role in kinase activation. New findings show that adenosine triphosphate (ATP) binding to Akt induces an intramolecular interaction between these phosphorylation sites and other domains in the protein, creating a cage around the phosphate group and restricting the access of phosphatases to these sites. ATP hydrolysis and substrate phosphorylation open the cage, which permits dephosphorylation and inactivation of the kinase. This switchlike mechanism provides important new insights into the biology of protein kinases.
许多信号转导途径包括蛋白激酶级联反应，其中每个组件的活性都受到磷酸化和去磷酸化的控制。现在已经揭示了涉及核苷酸结合的激酶调节的新层次。Akt 在两个调节位点的磷酸化在激酶激活中起主要作用。新的发现表明，三磷酸腺苷 (ATP) 与 Akt 的结合诱导这些磷酸化位点与蛋白质中其他结构域之间的分子内相互作用，在磷酸基团周围形成一个“笼子”，限制磷酸酶对这些位点的接近。ATP 水解和底物磷酸化打开“笼子”，从而允许激酶去磷酸化和失活。这种类似开关的机制为蛋白激酶的生物学提供了重要的新见解。
