Negative regulation of ErbB family receptor tyrosine kinases.
Negative regulation of ErbB family receptor tyrosine kinases.
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DOI：
10.1038/sj.bjc.6601500
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发表时间：
2004-01-26
影响因子：
8.8
通讯作者：
Carraway, K L 3rd
中科院分区：
文献类型：
--
作者：
Sweeney, C;Carraway, K L 3rd
EGF受体或生长因子受体酪氨酸激酶的ErbB家族的受体经常在各种实体瘤中过表达，并且其酪氨酸激酶活性的异常激活被认为有助于肿瘤生长和进展。已经投入了大量的努力来开发ErbB受体的抑制剂，并且抗体和小分子方法都表现出临床成功。最近，已经鉴定了许多内源性负调节蛋白，其抑制细胞中ErbB受体的信号传导活性。这些包括细胞内RING指E3泛素连接酶，如介导ErbB受体降解的cbl和Nrdp1，并可能包括多种分泌和跨膜蛋白，其抑制生长因子配体对受体的激活。确定肿瘤细胞抑制这些途径以促进其进展的程度以及内源性受体阴性调节途径的恢复是否可用于治疗益处将是有意义的。
Receptors of the EGF receptor or ErbB family of growth factor receptor tyrosine kinases are frequently overexpressed in a variety of solid tumours, and the aberrant activation of their tyrosine kinase activities is thought to contribute to tumour growth and progression. Much effort has been put into developing inhibitors of ErbB receptors, and both antibody and small-molecule approaches have exhibited clinical success. Recently, a number of endogenous negative regulatory proteins have been identified that suppress the signalling activity of ErbB receptors in cells. These include intracellular RING finger E3 ubiquitin ligases such as cbl and Nrdp1 that mediate ErbB receptor degradation, and may include a wide variety of secreted and transmembrane proteins that suppress receptor activation by growth factor ligands. It will be of interest to determine the extent to which tumour cells suppress these pathways to promote their progression, and whether restoration of endogenous receptor-negative regulatory pathways may be exploited for therapeutic benefit.