c-Cbl-dependent EphA2 protein degradation is induced by ligand binding.
c-Cbl-dependent EphA2 protein degradation is induced by ligand binding.
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发表时间：
2002-11
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通讯作者：
Jennifer Walker‐Daniels;D. Riese;M. Kinch
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作者：
Jennifer Walker‐Daniels;D. Riese;M. Kinch
EphA 2受体蛋白酪氨酸激酶在大量的人类癌症中过表达和功能改变。尽管其在癌症中的水平升高，但恶性细胞表面上的EphA 2表现出比非转化上皮细胞上的EphA 2更低的配体结合和酪氨酸磷酸化水平。在我们目前的研究中，我们证明了配体介导的刺激导致EphA 2被内化和降解。这种反应的机制涉及EphA 2的配体介导的自磷酸化，其促进EphA 2和c-Cbl衔接蛋白之间的缔合。我们还表明，c-Cbl促进刺激依赖性EphA 2降解。这些发现对于理解恶性细胞中EphA 2过表达的原因很重要，并为研究EphA 2作为治疗干预的潜在靶点提供了基础。
The EphA2 receptor protein tyrosine kinase is overexpressed and functionally altered in a large number of human carcinomas. Despite its elevated levels in cancer, the EphA2 on the surface of malignant cells demonstrates lower levels of ligand binding and tyrosine phosphorylation than the EphA2 on non-transformed epithelial cells. In our present study, we demonstrate that ligand-mediated stimulation causes EphA2 to be internalized and degraded. The mechanism of this response involves ligand-mediated autophosphorylation of EphA2, which promotes an association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl promotes stimulation-dependent EphA2 degradation. These findings are important for understanding the causes of EphA2 overexpression in malignant cells and provide a foundation for investigating EphA2 as a potential target for therapeutic intervention.