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胰岛素受体（IR）和胰岛素样生长因子1受体（IGF1R）结构表征的最新进展：对IR-IGF1R杂交受体调节剂设计的启示

Recent developments in the structural characterisation of the IR and IGF1R: implications for the design of IR-IGF1R hybrid receptor modulators.

作者信息

Turvey Samuel J, McPhillie Martin J, Kearney Mark T, Muench Stephen P, Simmons Katie J, Fishwick Colin W G

机构信息

Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds UK

School of Chemistry, University of Leeds UK

出版信息

RSC Med Chem. 2022 Feb 21;13(4):360-374. doi: 10.1039/d1md00300c. eCollection 2022 Apr 20.

DOI:10.1039/d1md00300c
PMID:35647546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9020618/
Abstract

The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) are dimeric disulfide-linked receptor tyrosine kinases, whose actions regulate metabolic and mitogenic signalling pathways inside the cell. It is well documented that in tissues co-expressing the IR and IGF1R, their respective monomers can heterodimerise to form IR-IGF1R hybrid receptors. Increased populations of the IR-IGF1R hybrid receptors are associated with several disease states, including type 2 diabetes and cancer. Recently, progress in the structural biology of IR and IGF1R has given insights into their structure-function relationships and mechanism of action. However, challenges in isolating IR-IGF1R hybrid receptors mean that their structural properties remain relatively unexplored. This review discusses the advances in the structural understanding of the IR and IGF1R, and how these discoveries can inform the design of small-molecule modulators of the IR-IGF1R hybrid receptors to understand their role in cell biology.

摘要

胰岛素受体（IR）和胰岛素样生长因子1受体（IGF1R）是通过二硫键连接的二聚体受体酪氨酸激酶，其作用调节细胞内的代谢和促有丝分裂信号通路。有充分的文献记载，在共表达IR和IGF1R的组织中，它们各自的单体可以异源二聚化形成IR-IGF1R杂合受体。IR-IGF1R杂合受体数量的增加与多种疾病状态相关，包括2型糖尿病和癌症。最近，IR和IGF1R的结构生物学进展为它们的结构-功能关系和作用机制提供了见解。然而，分离IR-IGF1R杂合受体面临的挑战意味着它们的结构特性仍相对未被探索。本综述讨论了对IR和IGF1R结构理解的进展，以及这些发现如何为设计IR-IGF1R杂合受体的小分子调节剂提供信息，以了解它们在细胞生物学中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/1f4b4ad0c20f/d1md00300c-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/97f64f6f4669/d1md00300c-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/9018f49a2d4f/d1md00300c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/527bc54e7909/d1md00300c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/4ae0f78cdda3/d1md00300c-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/48e1b7203fa6/d1md00300c-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/1f4b4ad0c20f/d1md00300c-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/97f64f6f4669/d1md00300c-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/31b42b12be0d/d1md00300c-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/3c02db2ed09a/d1md00300c-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/506fb473c352/d1md00300c-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/9018f49a2d4f/d1md00300c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/527bc54e7909/d1md00300c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/4ae0f78cdda3/d1md00300c-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/48e1b7203fa6/d1md00300c-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1f1/9020618/1f4b4ad0c20f/d1md00300c-f9.jpg

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