Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway
Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway
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DOI：
10.1074/jbc.m006969200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
Blenis, J
中科院分区：
文献类型：
--
作者：
Martin, KA;Schalm, SS;Blenis, J
核糖体S6激酶（ribosomalS 6 kinase，S6 K1）是一种重要的细胞翻译调节因子，通过40 S核糖体蛋白S6的磷酸化和5 '-末端寡嘧啶序列mRNA的调节而发挥作用。S6 K1也参与细胞大小的调节。我们最近鉴定了S6 K2，S6 K1的同源物，其在体外磷酸化S6，并在体内受磷脂酰肌醇3-激酶（PI 3-K）和哺乳动物雷帕霉素靶向通路的调节。在这里，我们的特点S6 K2调节PI 3-K信号中间体和比较其调节S6 K1，我们报告说，S6 K2激活类似于S6 K1的PI 3-K效应器磷酸肌醇依赖性激酶1，Cdc 42，Rac，和蛋白激酶C ζ，但S6 K2是更敏感的基础激活豆蔻酰化蛋白激酶C ζ比S6 K1。S6 K2的C-末端序列与S6 K1的不同。我们发现S6 K2的C-末端在S6 K2的调节中比S6 K1的C-末端起更大的作用，通过作为各种激动剂激活的有效抑制剂发挥作用。这些数据表明，S6 K1和S6 K2类似地被PI 3-K效应物激活，但S6 K2特有的序列有助于更强地抑制其激酶活性。了解这两个S6 K同源物的调节可以提供对这些激酶的生理作用的了解。
Ribosomal S6 kinase (S6K1), through phosphorylation of the 40 S ribosomal protein S6 and regulation of 5'-terminal oligopyrimidine tract mRNAs, is an important regulator of cellular translational capacity. S6K1 has also been implicated in regulation of cell size. We have recently identified S6K2, a homolog of S6K1, which phosphorylates S6 in vitro and is regulated by the phosphatidylinositide 3-kinase (PI3-K) and mammalian target of rapamycin pathways in vivo. Here, we characterize S6K2 regulation by PI3-K signaling intermediates and compare its regulation to that of S6K1, We report that S6K2 is activated similarly to S6K1 by the PI3-K effecters phosphoinositide-dependent kinase 1, Cdc42, Rac, and protein kinase C zeta but that S6K2 is more sensitive to basal activation by myristoylated protein kinase C zeta than is S6K1. The C-terminal sequence of S6K2 is divergent from that of S6K1, We find that the S6K2 C terminus plays a greater role in S6K2 regulation than does the S6K1 C terminus by functioning as a potent inhibitor of activation by various agonists, Removal of the S6K2 C terminus results in an enzyme that is hypersensitive to agonist-dependent activation. These data suggest that S6K1 and S6K2 are similarly activated by PI3-K effecters but that sequences unique to S6K2 contribute to stronger inhibition of its kinase activity. Understanding the regulation of the two S6K homologs may provide insight into the physiological roles of these kinases.