Department of Preclinical Sciences and Infectious Diseases, Poznan University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland.
Department of Virology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland.
Viruses. 2021 Jul 29;13(8):1488. doi: 10.3390/v13081488.
Insulin-like growth factor-1 (IGF-1) and the IGF-1 receptor (IGF-1R) belong to the insulin-like growth factor family, and IGF-1 activates intracellular signaling pathways by binding specifically to IGF-1R. The interaction between IGF-1 and IGF-1R transmits a signal through a number of intracellular substrates, including the insulin receptor substrate (IRS) and the Src homology collagen (Shc) proteins, which activate two major intracellular signaling pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways, specifically the extracellular signal-regulated kinase (ERK) pathways. The PI3K/AKT kinase pathway regulates a variety of cellular processes, including cell proliferation and apoptosis. IGF1/IGF-1R signaling also promotes cell differentiation and proliferation via the Ras/MAPK pathway. Moreover, upon IGF-1R activation of the IRS and Shc adaptor proteins, Shc stimulates Raf through the GTPase Ras to activate the MAPKs ERK1 and ERK2, phosphorylate and several other proteins, and to stimulate cell proliferation. The IGF-1 signaling pathway is required for certain viral effects in oncogenic progression and may be induced as an effect of viral infection. The mechanisms of IGF signaling in animal viral infections need to be clarified, mainly because they are involved in multifactorial signaling pathways. The aim of this review is to summarize the current data obtained from virological studies and to increase our understanding of the complex role of the IGF-1 signaling axis in animal virus infections.
胰岛素样生长因子-1（IGF-1）和 IGF-1 受体（IGF-1R）属于胰岛素样生长因子家族，IGF-1 通过特异性结合 IGF-1R 激活细胞内信号通路。IGF-1 与 IGF-1R 的相互作用通过许多细胞内底物传递信号，包括胰岛素受体底物（IRS）和Src 同源胶原（Shc）蛋白，它们激活两条主要的细胞内信号通路：磷脂酰肌醇 3-激酶（PI3K）/AKT 和丝裂原活化蛋白激酶（MAPK）通路，特别是细胞外信号调节激酶（ERK）通路。PI3K/AKT 激酶通路调节多种细胞过程，包括细胞增殖和凋亡。IGF1/IGF-1R 信号还通过 Ras/MAPK 通路促进细胞分化和增殖。此外，在 IGF-1R 激活 IRS 和 Shc 衔接蛋白后，Shc 通过 GTPase Ras 刺激 Raf 以激活 MAPKs ERK1 和 ERK2，磷酸化和几种其他蛋白质，并刺激细胞增殖。IGF-1 信号通路是致癌进展中某些病毒效应所必需的，并且可能作为病毒感染的效应而被诱导。需要阐明 IGF 信号在动物病毒感染中的机制，主要是因为它们涉及多因素信号通路。本综述的目的是总结从病毒学研究中获得的现有数据，并提高我们对 IGF-1 信号轴在动物病毒感染中的复杂作用的理解。
