Chen Ping-Hung, Yao Huiyu, Huang Lily Jun-Shen
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Front Endocrinol (Lausanne). 2017 May 1;8:78. doi: 10.3389/fendo.2017.00078. eCollection 2017.
Type I and II cytokine receptors are cell surface sensors that bind cytokines in the extracellular environment and initiate intracellular signaling to control processes such as hematopoiesis, immune function, and cellular growth and development. One key mechanism that regulates signaling from cytokine receptors is through receptor endocytosis. In this mini-review, we describe recent advances in endocytic regulations of cytokine receptors, focusing on new paradigms by which PI3K controls receptor endocytosis through both kinase activity-dependent and -independent mechanisms. These advances underscore the notion that the p85 regulatory subunit of PI3K has functions beyond regulating PI3K kinase activity, and that PI3K plays both positive and negative roles in receptor signaling. On the one hand, the PI3K/Akt pathway controls various aspects downstream of cytokine receptors. On the other hand, it stimulates receptor endocytosis and downregulation, thus contributing to signaling attenuation.
I型和II型细胞因子受体是细胞表面传感器，它们在细胞外环境中结合细胞因子，并启动细胞内信号传导以控制诸如造血、免疫功能以及细胞生长和发育等过程。调节细胞因子受体信号传导的一个关键机制是通过受体内吞作用。在这篇小型综述中，我们描述了细胞因子受体内吞调节的最新进展，重点关注PI3K通过激酶活性依赖性和非依赖性机制控制受体内吞作用的新范例。这些进展强调了PI3K的p85调节亚基具有超出调节PI3K激酶活性的功能这一观点，并且PI3K在受体信号传导中发挥着正负两方面的作用。一方面，PI3K/Akt途径控制细胞因子受体下游的各个方面。另一方面，它刺激受体内吞作用和下调，从而导致信号衰减。
