Hu Huimin, Liu Yanwei, Jiang Tao
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili, Dongcheng, Beijing, 100050, People's Republic of China.
Tumour Biol. 2015 Mar;36(3):1423-8. doi: 10.1007/s13277-015-3287-4. Epub 2015 Mar 7.
Cancer is the greatest challenge to human health in our era. Perturbations of receptor tyrosine kinase (RTK) function contribute to a large chunk of cancer etiology. Current evidence supports that mutations in RTKs mediate receptor dimerization and result in ligand-independent kinase activity and tumorigenesis, indicating that mutation-introduced receptor dimerization is a critical component of oncogenesis RTK mutations. However, there are no specialized reviews of this important principle. In the current review, we discuss the physiological and harmless RTK function and subsequently examine mutation-introduced dimerization of RTKs and the role of these mutations in tumorigenesis. We also summarize the protein structure characteristics that are important for dimerization and introduce research methods and tools to predict and validate the existence of oncogenic mutations introduced by dimerization in RTKs.
癌症是我们这个时代人类健康面临的最大挑战。受体酪氨酸激酶（RTK）功能的紊乱在很大程度上导致了癌症的病因。目前的证据表明，RTK中的突变介导受体二聚化，并导致非配体依赖性激酶活性和肿瘤发生，这表明突变引入的受体二聚化是肿瘤发生RTK突变的关键组成部分。然而，目前尚无关于这一重要原理的专门综述。在本综述中，我们讨论了RTK的生理和无害功能，随后研究了突变引入的RTK二聚化及其在肿瘤发生中的作用。我们还总结了对二聚化很重要的蛋白质结构特征，并介绍了预测和验证RTK中二聚化引入的致癌突变存在的研究方法和工具。
