Down-regulation of MET, the receptor for hepatocyte growth factor
Down-regulation of MET, the receptor for hepatocyte growth factor
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DOI：
10.1038/sj.onc.1204475
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发表时间：
2001-05-17
期刊：
影响因子：
8
通讯作者：
Clague, MJ
中科院分区：
文献类型：
--
作者：
Hammond, DE;Urbé, S;Clague, MJ
激活的酪氨酸激酶受体的配体依赖性降解提供了一种可以减弱有丝分裂信号的手段。在许多细胞类型中，酪氨酸激酶受体Met的配体依赖性降解完全依赖于26S蛋白酶体的活性（Jeffers等人，1997b）。我们现在表明，降解还需要运输到内体晚期的室室和酸依赖性蛋白酶的活性，这是由动力蛋白（K44A）的显性阴性形式和液泡- atp酶抑制剂康那霉素的作用决定的。我们表明，在蛋白酶体抑制剂乳糖蛋白酶的存在下，Met不能从质膜重新分布到细胞内。这一观察结果与蛋白酶体活性是Met内化所需的解释最为一致，而蛋白酶体活性仅间接用于Met的降解。
The ligand-dependent degradation of activated tyrosine kinase receptors provides a means by which mitogenic signalling can be attenuated. In many cell types the ligand-dependent degradation of the tyrosine kinase receptor Met is completely dependent on the activity of the 26S proteasome (Jeffers et al,, 1997b), We now show that degradation also requires trafficking to late endosomal compartments and the activity of acid dependent proteases as determined by the effects of a dominant negative form of dynamin (K44A) and a vacuolar-ATPase inhibitor, concanamycin, We show that in the presence of the proteasome inhibitor lactacystin, Met fails to redistribute from the plasma membrane to intracellular compartments. This observation is most consistent with the interpretation that proteasome activity is required for Met internalization and only indirectly for its degradation.