气候变化领域集成服务门户(CCPortal): BMP heterodimers signal via distinct type I receptor class functions

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DOI	10.1073/pnas.2017952118
	BMP heterodimers signal via distinct type I receptor class functions
	Tajer B.; Dutko J.A.; Little S.C.; Mullins M.C.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Heterodimeric TGF-β ligands outperform homodimers in a variety of developmental, cell culture, and therapeutic contexts; however, the mechanisms underlying this increased potency remain uncharacterized. Here, we use dorsal-ventral axial patterning of the zebrafish embryo to interrogate the BMP2/7 heterodimer signaling mechanism. We demonstrate that differential interactions with BMP antagonists do not account for the reduced signaling ability of homodimers. Instead, we find that while overexpressed BMP2 homodimers can signal, they require two nonredundant type I receptors, one from the Acvr1 subfamily and one from the Bmpr1 subfamily. This implies that all BMP signaling within the zebrafish gastrula, even BMP2 homodimer signaling, requires Acvr1. This is particularly surprising as BMP2 homodimers do not bind Acvr1 in vitro. Furthermore, we find that the roles of the two type I receptors are subfunctionalized within the heterodimer signaling complex, with the kinase activity of Acvr1 being essential, while that of Bmpr1 is not. These results suggest that the potency of the Bmp2/7 heterodimer arises from the ability to recruit both Acvr1 and Bmpr1 into the same signaling complex. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	BMP; Bone morphogenetic protein; Heterodimers; Signaling; Zebrafish
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179933
作者单位	Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Tajer B.,Dutko J.A.,Little S.C.,et al. BMP heterodimers signal via distinct type I receptor class functions[J],2021,118(15).
APA	Tajer B.,Dutko J.A.,Little S.C.,&Mullins M.C..(2021).BMP heterodimers signal via distinct type I receptor class functions.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Tajer B.,et al."BMP heterodimers signal via distinct type I receptor class functions".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).