Department of Microbiology and Immunology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, United States.
Baltimore VA Medical Center, Baltimore, MD, United States.
Front Immunol. 2018 May 15;9:1037. doi: 10.3389/fimmu.2018.01037. eCollection 2018.
In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.
在这篇纪念 William E. Paul 博士的历史性论文中，我们描述了最初发现的白细胞介素 4（IL-4）刺激的酪氨酸磷酸化的主要底物之一。我们进一步描述了如何将这种“IL-4 诱导的磷酸化底物”（4PS）鉴定为胰岛素受体底物（IRS）家族的一员，该家族的大型衔接蛋白将 IL-4 和胰岛素受体连接到磷脂酰肌醇 3'激酶途径以及其他下游信号途径的激活。4PS/IRS 途径对 IL-4 诱导增殖和抑制细胞凋亡的早期模型的相对贡献，与我们对 IRS 家族成员产生的正、负调节途径之间的复杂相互作用的最新理解进行了比较，这些调节途径影响过敏反应。
