Warren Carmen M, Landgraf Ralf
University of California Los Angeles, Department of Medicine, Biological Chemistry, United States.
Cell Signal. 2006 Jul;18(7):923-33. doi: 10.1016/j.cellsig.2005.12.007. Epub 2006 Feb 7.
The four known ERBB receptors in humans are involved in a broad range of cellular responses, and their deregulation is a significant aspect in a large number of disease states. However, their mechanism of action and modes of control are still poorly understood. This is largely due to the fact that the control of ERBB activity is a multilayered process with significant differences between the various ERBB members. In contrast to other receptor tyrosine kinases, the kinase domain of EGFR (ERBB1) does not require phosphorylation for activation. Consequently, the overall activation state of the receptor is controlled by constant balancing of activity favoring and activity suppressing actions within the receptor molecule. Influences of the membrane microenvironment and context dependent interactions with varying sets of signaling partners are superimposed on this system of intramolecular checks and balances. We will discuss current models of the control of ERBB signaling with an emphasis on the multilayered nature of activation control and aspects that give rise to diversity between ERBB receptors.
人类已知的四种ERBB受体参与了广泛的细胞反应，其失调是许多疾病状态的一个重要方面。然而，它们的作用机制和调控模式仍知之甚少。这主要是因为ERBB活性的调控是一个多层次的过程，不同的ERBB成员之间存在显著差异。与其他受体酪氨酸激酶不同，表皮生长因子受体（ERBB1）的激酶结构域不需要磷酸化即可激活。因此，受体的整体激活状态是通过受体分子内促进活性和抑制活性作用的持续平衡来控制的。膜微环境的影响以及与不同信号伴侣组的上下文依赖性相互作用叠加在这个分子内制衡系统之上。我们将讨论当前ERBB信号调控模型，重点关注激活调控的多层次性质以及导致ERBB受体之间多样性的方面。
