Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
Prog Mol Biol Transl Sci. 2023;194:79-107. doi: 10.1016/bs.pmbts.2022.06.020. Epub 2022 Jul 13.
Insulin signaling controls multiple aspects of animal physiology. At the cell surface, insulin binds and activates the insulin receptor (IR), a receptor tyrosine kinase. Insulin promotes a large conformational change of IR and stabilizes the active conformation. The insulin-activated IR triggers signaling cascades, thus controlling metabolism, growth, and proliferation. The activated IR undergoes internalization by clathrin- or caveolae-mediated endocytosis. The IR endocytosis plays important roles in insulin clearance from blood, and distribution and termination of the insulin signaling. Despite decades of extensive studies, the mechanism and regulation of IR endocytosis and its contribution to pathophysiology remain incompletely understood. Here we discuss recent findings that provide insights into the molecular mechanisms and regulatory pathways that mediate the IR endocytosis.
胰岛素信号控制着动物生理学的多个方面。在细胞表面，胰岛素与胰岛素受体 (IR) 结合并激活它，IR 是一种受体酪氨酸激酶。胰岛素促进 IR 的构象发生巨大变化并稳定其活性构象。胰岛素激活的 IR 触发信号级联反应，从而控制代谢、生长和增殖。激活的 IR 通过网格蛋白或小窝介导的内吞作用被内化。IR 内化在胰岛素从血液中清除、胰岛素信号的分布和终止中起着重要作用。尽管经过几十年的广泛研究，但 IR 内化的机制和调节及其对病理生理学的贡献仍不完全清楚。本文讨论了最近的发现，这些发现为介导 IR 内化的分子机制和调节途径提供了新的见解。
