The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, ul. Instytucka 3, 05-110 Jabłonna, Poland.
Int J Mol Sci. 2018 Jun 22;19(7):1843. doi: 10.3390/ijms19071843.
The growth hormone (GH) plays a key role in the regulation of metabolic processes in an organism. Determination of the correct structure and functioning of the growth hormone receptor (GHR) allowed for a more detailed research of its post-receptor regulators, which substantially influences its signal transduction. This review is focused on the description of the post-receptor inhibitors of the GHR-JAK2-STAT pathway, which is one of the most important pathways in the transduction of the somatotropic axis signal. The aim of this review is the short characterization of the main post-receptor inhibitors, such as: cytokine-inducible SH2-containing protein (CIS), Suppressors of Cytokine Signaling (SOCS) 1, 2 and 3, sirtuin 1 (SIRT1), protein inhibitors of activated STAT (PIAS) 1, 3 and PIAS4, protein tyrosine phosphatases (PTP) 1B and H1, Src homology 2 (SH2) domain containing protein tyrosine phosphatase (SHP) 1, 2 and signal regulatory protein (SIRP) α1. The equilibrium between these regulators activity and inhibition is of special concern because, as many studies showed, even slight imbalance may disrupt the GH activity causing serious diseases. The regulation of the described inhibitors expression and activity may be a point of interest for pharmaceutical industry.
生长激素(GH)在调节生物体的代谢过程中起着关键作用。生长激素受体(GHR)的正确结构和功能的确定,使得对其受体后调节剂的更详细研究成为可能,这对其信号转导有很大影响。本综述重点描述了 GHR-JAK2-STAT 途径的受体后抑制剂,该途径是转导生长激素轴信号的最重要途径之一。本综述的目的是简要描述主要的受体后抑制剂,如:细胞因子诱导的 SH2 结构域蛋白(CIS)、细胞因子信号转导抑制物(SOCS)1、2 和 3、沉默调节蛋白 1(SIRT1)、激活 STAT 的蛋白抑制剂(PIAS)1、3 和 PIAS4、蛋白酪氨酸磷酸酶(PTP)1B 和 H1、Src 同源 2(SH2)结构域含蛋白酪氨酸磷酸酶(SHP)1、2 和信号调节蛋白(SIRP)α1。这些调节剂的活性和抑制之间的平衡特别值得关注,因为正如许多研究表明的那样,即使是轻微的失衡也可能破坏 GH 的活性,导致严重的疾病。描述的抑制剂的表达和活性的调节可能是制药工业的一个关注点。