Insulin-like Growth Factor 1 Receptor  (胰岛素样生长因子 1 受体)

胰岛素样生长因子 (IGF) 系统包括两个主要受体IGF-IR 和 IGF-IIR。IGF-IR 和IGF-IIR 都是结构和功能完全不同的跨膜糖蛋白。IGF-IR 是由两个相同的 α 亚基和两个相同的 β 亚基组成的四聚体。在结构上，IGF-IR 与胰岛素受体相似，同源性为60%。IGFs和胰岛素能够相互交叉结合受体，尽管其结合亲和力比首选配体弱得多。IGF-IR和胰岛素受体可以杂交形成混合受体，即由IGF-IR和胰岛素受体的α/β 亚基异源二聚体组成。IGF-IIR (M6P受体) 是单体形式。在该受体的胞外区域发现了三个配体结合区域，一个是与 IGF-II 结合的区域，另两个分别是含有甘露糖-6-磷酸 (M6P) 和转化生长因子 TGF-β 休眠形式的结合域。IGF-IIR 对 IGF-II 配体具有结合高亲和力，但它是一种非信号转导受体。 IGFs 广泛表达，并通过与 IGF-IR 结合以自分泌/旁分泌方式起作用，如调节细胞增殖、分化、凋亡和转化。IGF 配体与IGF-IR 的结合激活了受体的酪氨酸激酶活性，从而触发了信号转导途径中涉及的许多分子之间的级联反应，包括PI3K-Akt 途径。IGF-IIR 没有酪氨酸激酶活性，被认为是 IGF-II 的拮抗剂，通过与 IGF-II 结合来降低其生物活性。据报道，IGF-IR 信号通路的失调可导致多种疾病，包括糖尿病视网膜病变、糖尿病肾病、年龄相关性黄斑变性、心血管疾病、衰老和各种癌症。

The Insulin-like growth factor (IGF) system comprises two main receptors, IGF-IR and IGF-IIR. Both IGF-IR and IGF-IIR are transmembrane glycoproteins that differ completely in their structure and function. IGF-IR is a tetramer of two equal α-subunits and two equal β-subunits. Structurally, IGF-IR resembles the insulin receptor with 60% homology. IGFs and insulin are proficient to cross-bind to each other's receptor, although with much weaker binding affinity than that for the preferred ligand. IGF-IR and insulin receptor (IR) can hybridize to form a heterodimer composed of one α-subunit and one β-subunit of each receptor. IGF-IIR (M6P receptor) is monomeric. In the extracellular domain of the receptor, three ligand-binding regions are found one for IGF-II binding and two for proteins containing mannose-6-phosphate (M6P) and the dormant form of transforming growth factor- (TGF-) β. IGF-IIR has high affinity for binding the IGF-II ligand but is a nonsignalling receptor. The IGFs are expressed ubiquitously and act in an autocrine/paracrine manner which including regulate cell proliferation, differentiation, apoptosis, and transformation through binding to the IGF-IR. Binding of IGF ligands to IGF-IR activates the receptor's tyrosine kinase activity, which triggers a cascade of reactions among a number of molecules involved in the signal transduction pathway, including the phosphatidyl-inositol-3 kinase (PI3K)-protein kinase B (Akt) pathway. IGF-IIR has no tyrosine kinase activity is considered to act like an antagonist to IGF-II, reducing its biologic activity by binding to IGF-II. Deregulation of IGF-IR signalling has been reported to contribute to a variety of diseases including diabetic retinopathy, diabetic nephropathy, age-related macular degeneration, cardiovascular disease, and aging and in a variety of cancers.