维持Raf-1磷酸化和激酶活性需要14-3-3蛋白。
14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity.
作者信息
Thorson J A, Yu L W, Hsu A L, Shih N Y, Graves P R, Tanner J W, Allen P M, Piwnica-Worms H, Shaw A S
机构信息
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri, USA.
出版信息
Mol Cell Biol. 1998 Sep;18(9):5229-38. doi: 10.1128/MCB.18.9.5229.
By binding to serine-phosphorylated proteins, 14-3-3 proteins function as effectors of serine phosphorylation. The exact mechanism of their action is, however, still largely unknown. Here we demonstrate a requirement for 14-3-3 for Raf-1 kinase activity and phosphorylation. Expression of dominant negative forms of 14-3-3 resulted in the loss of a critical Raf-1 phosphorylation, while overexpression of 14-3-3 resulted in enhanced phosphorylation of this site. 14-3-3 levels, therefore, regulate the stoichiometry of Raf-1 phosphorylation and its potential activity in the cell. Phosphorylation of Raf-1, however, was insufficient by itself for kinase activity. Removal of 14-3-3 from phosphorylated Raf abrogated kinase activity, whereas addition of 14-3-3 restored it. This supports a paradigm in which the effects of phosphorylation on serine as well as tyrosine residues are mediated by inducible protein-protein interactions.
通过与丝氨酸磷酸化蛋白结合，14 - 3 - 3蛋白作为丝氨酸磷酸化的效应器发挥作用。然而，其确切的作用机制在很大程度上仍不清楚。在此我们证明了Raf - 1激酶活性和磷酸化需要14 - 3 - 3。14 - 3 - 3显性负性形式的表达导致关键的Raf - 1磷酸化丧失，而14 - 3 - 3的过表达导致该位点磷酸化增强。因此，14 - 3 - 3水平调节Raf - 1磷酸化的化学计量及其在细胞中的潜在活性。然而，Raf - 1的磷酸化本身对于激酶活性是不足的。从磷酸化的Raf中去除14 - 3 - 3消除了激酶活性，而添加14 - 3 - 3则恢复了活性。这支持了一种模式，即丝氨酸以及酪氨酸残基上的磷酸化作用是由可诱导的蛋白质 - 蛋白质相互作用介导的。
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