Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells
Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells
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DOI：
10.1074/jbc.m210998200
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发表时间：
2003-05-09
影响因子：
4.8
通讯作者：
Codogno, P
中科院分区：
文献类型：
--
作者：
Pattingre, S;Bauvy, C;Codogno, P
ERK 1/2的活化通过以氨基酸依赖性方式促进Galpha相互作用蛋白（GAIP）的磷酸化来刺激人结肠癌细胞系HT-29中的大自噬（Ogier-Denis，E.，Pattingre，S.，El Benna，J.，和Codogno，P.（2000）J.Biol.Chem.275，39090-39095）。在这里，我们表明，ERK 1/2激活金精三羧酸（ATA）处理诱导GAIP的磷酸化在一个氨基酸依赖性的方式。因此，ATA攻击增加了巨自噬的速率，而表皮生长因子并没有显着影响巨自噬和GAIP磷酸化状态。事实上，ATA激活了ERK 1/2信号通路，而表皮生长因子刺激了ERK 1/2通路和I类磷酸肌醇3-激酶通路，已知其降低了巨自噬的速率。氨基酸通过抑制激酶Raf-1的活化来干扰ATA诱导的大自噬。Ras/Raf-1/ERK 12信号通路在GAIP-和氨基酸依赖性控制巨自噬中的作用在表达Ras（G12 V，T35 S）突变体的HT-29细胞中得到证实。与蛋白磷酸酶2A抑制剂冈田酸类似，氨基酸维持Ser（259）的磷酸化，其参与Raf-1的负调节。总之，这些结果增加了一个新的目标，在肠细胞中的宏观自噬的氨基酸信号依赖性控制。
Activation of ERK1/2 stimulates macroautophagy in the human colon cancer cell line HT-29 by favoring the phosphorylation of the Galpha-interacting protein (GAIP) in an amino acid-dependent manner (Ogier-Denis, E., Pattingre, S., El Benna, J., and Codogno, P. (2000) J. Biol. Chem. 275, 39090-39095). Here we show that ERK1/2 activation by aurintricarboxylic acid (ATA) treatment induces the phosphorylation of GAIP in an amino acid-dependent manner. Accordingly, ATA challenge increased the rate of macroautophagy, whereas epidermal growth factor did not significantly affect macroautophagy and GAIP phosphorylation status. In fact, ATA activated the ERK1/2 signaling pathway, whereas epidermal growth factor stimulated both the ERK1/2 pathway and the class I phosphoinositide 3-kinase pathway, known to decrease the rate of macroautophagy. Amino acids interfered with the ATA-induced macroautophagy by inhibiting the activation of the kinase Raf-1. The role of the Ras/Raf-1/ERK1/2 signaling pathway in the GAIP- and amino acid-dependent control of macroautophagy was confirmed in HT-29 cells expressing the Ras(G12V, T35S) mutant. Similar to the protein phosphatase 2A inhibitor okadaic acid, amino acids sustained the phosphorylation of Ser(259), which is involved in the negative regulation of Raf-1. In conclusion, these results add a novel target to the amino acid signaling-dependent control of macroautophagy in intestinal cells.