Regulation of the catalytic activity of the EGF receptor.

Regulation of the catalytic activity of the EGF receptor.
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DOI:
10.1016/j.sbi.2011.07.007
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发表时间:
2011-12
影响因子:
6.8
通讯作者:
Kuriyan J
Kuriyan J
中科院分区:
生物学2区
文献类型:
--
作者:
Endres NF;Engel K;Das R;Kovacs E;Kuriyan J

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表皮生长因子受体(EGFR)是一种参与细胞生长的受体酪氨酸激酶,在癌症中经常被错误调节。最近的几项研究强调了其调节所涉及的独特结构机制。一些阐明的重要作用,跨膜段和跨膜螺旋在稳定活化的不对称激酶二聚体,并建议其激活机制可能是保守的其他人类EGFR相关受体。其他研究为两个长期观察到的但知之甚少的现象提供了新的解释,即配体结合的明显异质性和非配体依赖性二聚体的形成。对EGFR细胞内调节因子所利用的变构机制的新见解为变构位点可用作药物开发的靶点提供了希望。
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in cell growth that is often misregulated in cancer. Several recent studies highlight the unique structural mechanisms involved in its regulation. Some elucidate the important role that the juxtamembrane segment and the transmembrane helix play in stabilizing the activating asymmetric kinase dimer, and suggest that its activation mechanism is likely to be conserved amongst the other human EGFR-related receptors. Other studies provide new explanations for two long observed, but poorly understood phenomena, the apparent heterogeneity in ligand binding and the formation of ligand-independent dimers. New insights into the allosteric mechanisms utilized by intracellular regulators of EGFR provide hope that allosteric sites could be used as targets for drug development.
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