PHOSPHORYLATION OF RIBOSOMAL-PROTEIN S6 IS INHIBITORY FOR AUTOPHAGY IN ISOLATED RAT HEPATOCYTES
PHOSPHORYLATION OF RIBOSOMAL-PROTEIN S6 IS INHIBITORY FOR AUTOPHAGY IN ISOLATED RAT HEPATOCYTES
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DOI：
10.1074/jbc.270.5.2320
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发表时间：
1995-02-03
影响因子：
4.8
通讯作者：
MEIJER, AJ
中科院分区：
文献类型：
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作者：
BLOMMAART, EFC;LUIKEN, JJFP;MEIJER, AJ
在大鼠肝细胞中，自噬被氨基酸抑制，胰岛素和细胞肿胀促进氨基酸的抑制，导致自噬蛋白水解抑制的每一种情况都被发现与一个31 kda蛋白的磷酸化有关，我们确定该蛋白为核糖体蛋白S6。亮氨酸、酪氨酸和苯丙氨酸的组合能有效抑制自噬蛋白水解，对S6磷酸化的刺激尤其有效，蛋白水解抑制百分比与Se磷酸化程度呈线性关系，说明自噬抑制与S6磷酸化受同一信号转导通路控制。氨基酸的存在刺激S6磷酸化是由于S6激酶的激活，而不是由于S6磷酸酶的抑制。氨基酸对电注射胞质[C-14]蔗糖的自噬蛋白水解和自噬隔离的抑制作用可以被雷帕霉素部分阻止，雷帕霉素是一种已知能抑制p70 S6激酶活化的化合物，此外，雷帕霉素部分抑制蛋白质合成的速度。我们得出结论，通过自噬和蛋白质合成途径的通量以相反的方式受到S6磷酸化程度的调节。讨论了S6磷酸化引起自噬抑制的可能机制。
In rat hepatocytes, autophagy is known to be inhibited by amino acids, Insulin and cell swelling promote inhibition by amino acids, Each of the conditions leading to inhibition of autophagic proteolysis was found to be associated with phosphorylation of a 31-kDa protein that we identified as ribosomal protein S6. A combination of leucine, tyrosine, and phenylalanine, which efficiently inhibits autophagic proteolysis, was particularly effective in stimulating S6 phosphorylation, The relationship between the percentage inhibition of proteolysis and the degree of Se phosphorylation was linear, Thus, inhibition of autophagy and phosphorylation of S6 are under the control of the same signal transduction pathway, Stimulation of S6 phosphorylation by the presence of amino acids was due to activation of S6 kinase and not to inhibition of S6 phosphatase.The inhibition by amino acids of both autophagic proteolysis and autophagic sequestration of electro-injected cytosolic [C-14]sucrose was partially prevented by rapamycin, a compound known to inhibit activation of p70 S6 kinase, In addition, rapamycin partially inhibited the rate of protein synthesis.We conclude that the fluxes through the autophagic and protein synthetic pathways are regulated in an opposite manner by the degree to which S6 is phosphorylated. Possible mechanisms by which S6 phosphorylation can cause inhibition of autophagy are discussed.