Bublil Erez M, Yarden Yosef
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Curr Opin Cell Biol. 2007 Apr;19(2):124-34. doi: 10.1016/j.ceb.2007.02.008. Epub 2007 Feb 20.
The ErbB receptor tyrosine kinases evolved as key regulatory entities enabling the extracellular milieu to communicate with the intracellular machinery to bring forth the appropriate biological response in an ever-changing environment. Since its discovery, many aspects of the ErbB family have been deciphered, with emphasis on aberration of signaling in human diseases. However, only now, with the availability of the atomic coordinates of these receptors, can we construct a comprehensive model of the mechanisms underlying ligand-induced receptor dimerization and subsequent tyrosine kinase activation. Furthermore, the recent introduction of new high-throughput screening methodologies, combined with the materialization of a systems biology perspective, reveals an overwhelming network complexity, enabling robust signaling and evolvability. This knowledge is likely to impact our view of diseases as system perturbations and resistance to ErbB-targeted therapeutics as manifestations of robustness.
表皮生长因子受体（ErbB）酪氨酸激酶逐渐成为关键的调控实体，使细胞外环境能够与细胞内机制进行沟通，从而在不断变化的环境中引发适当的生物学反应。自发现以来，ErbB家族的许多方面已被破解，重点是人类疾病中信号传导的异常。然而，直到现在，随着这些受体原子坐标的可得，我们才能构建一个关于配体诱导受体二聚化及随后酪氨酸激酶激活的潜在机制的综合模型。此外，最近新的高通量筛选方法的引入，结合系统生物学观点的实现，揭示了极其复杂的网络，实现了强大的信号传导和进化能力。这些知识可能会影响我们对疾病的看法，即疾病是系统扰动，而对ErbB靶向治疗的抗性是稳健性的表现。
