骨形态发生蛋白信号传导:途径及其调控。

IF 3.3 3区 生物学
Genetics Pub Date : 2023-12-20 DOI:10.1093/genetics/iyad200
Takuya Akiyama, Laurel A Raftery, Kristi A Wharton
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引用次数: 0

摘要

20 世纪 60 年代中期,人们首次在骨提取物中发现骨形态发生蛋白(BMPs)具有诱导异位骨的显著能力。20 世纪 80 年代末,果蝇基因 decapentaplegic(dpp)首次被发现与哺乳动物的 BMP2/BMP4 具有序列相似性,由此可见,分泌型 BMP 配体可以介导骨形成以外的过程。在这一发现之后,果蝇遗传学家和哺乳动物生物化学家合作,利用各自模型系统的优势,确定了 BMP 信号转导成分,并描绘了信号转导途径。果蝇能够相对容易地进行遗传修饰筛选,这对于确定 BMP 信号转导和相关转化生长因子-β/活素信号转导途径的细胞内信号转导物至关重要。这种筛选还发现了大量编码该通路其他核心信号元件和调控因子的基因。在这篇综述中,我们回顾了这一激动人心的基因发现时期,并讨论了该领域在过去 30 年中取得的进展。我们了解到,虽然 BMP 核心通路非常简单,由 3 个部分(配体、受体和信号转导子)组成,但在这一通路的多功能性背后,存在着多层调控,以确保精确的组织特异性信号输出。我们提供了这些发现的样本,并强调了许多有待解答的问题,以全面了解 BMP 信号传导的复杂性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bone morphogenetic protein signaling: the pathway and its regulation.
In the mid-1960s, bone morphogenetic proteins (BMPs) were first identified in the extracts of bone to have the remarkable ability to induce heterotopic bone. When the Drosophila gene decapentaplegic (dpp) was first identified to share sequence similarity with mammalian BMP2/BMP4 in the late-1980s, it became clear that secreted BMP ligands can mediate processes other than bone formation. Following this discovery, collaborative efforts between Drosophila geneticists and mammalian biochemists made use of the strengths of their respective model systems to identify BMP signaling components and delineate the pathway. The ability to conduct genetic modifier screens in Drosophila with relative ease was critical in identifying the intracellular signal transducers for BMP signaling and the related transforming growth factor-beta/activin signaling pathway. Such screens also revealed a host of genes that encode other core signaling components and regulators of the pathway. In this review, we provide a historical account of this exciting time of gene discovery and discuss how the field has advanced over the past 30 years. We have learned that while the core BMP pathway is quite simple, composed of 3 components (ligand, receptor, and signal transducer), behind the versatility of this pathway lies multiple layers of regulation that ensures precise tissue-specific signaling output. We provide a sampling of these discoveries and highlight many questions that remain to be answered to fully understand the complexity of BMP signaling.
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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