Holbro Thomas, Hynes Nancy E
Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland.
Annu Rev Pharmacol Toxicol. 2004;44:195-217. doi: 10.1146/annurev.pharmtox.44.101802.121440.
The epidermal growth factor (EGF)-related peptides bind the ErbB receptors, inducing the formation of different homo- and heterodimers. Receptor dimerization promotes activation of the intrinsic kinase, leading to phosphorylation of specific tyrosines located in the ErbB's cytoplasmic region. These phosphorylated residues serve as docking sites for a variety of signaling molecules whose recruitment stimulates intracellular signaling cascades, which ultimately control diverse genetic programs. Particular ligand-receptor complexes have essential roles in embryonic development as well as in the adult. Finally, ErbB receptors are being pursued as therapeutic targets because aberrant ErbB activity has been observed in many human cancers. In this review, we discuss these data in more detail, illustrating the importance of tightly regulated ErbB signaling throughout life.
表皮生长因子（EGF）相关肽与表皮生长因子受体（ErbB）结合，诱导形成不同的同二聚体和异二聚体。受体二聚化促进内在激酶的激活，导致位于ErbB胞质区域的特定酪氨酸磷酸化。这些磷酸化残基作为多种信号分子的停靠位点，这些信号分子的募集刺激细胞内信号级联反应，最终控制各种基因程序。特定的配体-受体复合物在胚胎发育以及成体中都起着至关重要的作用。最后，由于在许多人类癌症中都观察到ErbB活性异常，因此ErbB受体正被作为治疗靶点进行研究。在本综述中，我们将更详细地讨论这些数据，阐明在整个生命过程中严格调控ErbB信号传导的重要性。
