Polypeptide Hormone Laboratory, McGill University and the Royal Victoria Hospital, Montreal, Quebec, Canada H3A2B2.
J Cell Biochem. 2010 Apr 15;109(6):1103-8. doi: 10.1002/jcb.22505.
There is now abundant evidence that the intracellular concentration of the EGFR and many other receptors for peptide hormones and growth factors is important for the temporal and spatial regulation of cell signaling. Spatial control is achieved by the selective compartmentalization of signaling components into endosomes. However further control may be effected by sequestration into sub-domains within a given organelle such as membrane rafts which are dynamic, nano scale structures rich in cholesterol and sphingolipids. Current data suggest the presence of EGFRs in non-caveolae membrane rafts. High doses of EGF seem to promote the sorting of EGFR to late endosomes through a raft/cholesterol dependant mechanism, implicating them in EGFR degradation. However our work and that of others has led us to propose a model in which membrane rafts in late endosomes sequester highly active EGFR leading to the recruitment and activation of MAPK in this compartment.
现在有大量证据表明，细胞内表皮生长因子受体（EGFR）和许多其他肽激素和生长因子受体的浓度对于细胞信号转导的时空调节非常重要。空间控制是通过将信号成分选择性地分隔到内涵体中来实现的。然而，进一步的控制可能通过将其隔离到特定细胞器内的子域来实现，例如富含胆固醇和鞘脂的动态纳米级结构的膜筏。目前的数据表明，EGFR 存在于非窖蛋白的膜筏中。高剂量的表皮生长因子（EGF）似乎通过一种依赖于筏/胆固醇的机制促进 EGFR 的分拣到晚期内涵体中，这暗示它们参与了 EGFR 的降解。然而，我们的工作和其他人的工作使我们提出了一个模型，即晚期内涵体中的膜筏将高活性的 EGFR 隔离，导致 MAPK 在这个隔室中的募集和激活。
