TGF-beta signalling is mediated by two autonomously functioning T beta RI:T beta RII pairs

doi:10.1038/emboj.2011.54

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	TGF-beta signalling is mediated by two autonomously functioning T beta RI:T beta RII pairs
	Huang, Tao 1; David, Laurent 2; Mendoza, Valentin 3; Yang, Yong 4; Villarreal, Maria 1; De, Keya 5; Sun, LuZhe 5; Fang, Xiaohong 4; Lopez-Casillas, Fernando 3; Wrana, Jeffrey L.2,6
刊名	EMBO JOURNAL
	2011-04-06
卷号	30 期号:7 页码:1263-1276
关键词	Signal Transduction Signalling t Beta Ri t Beta Rii Tgf-beta
ISSN号	0261-4189
DOI	10.1038/emboj.2011.54
英文摘要	Transforming growth factor (TGF)-beta s are dimeric polypeptides that have vital roles in regulating cell growth and differentiation. They signal by assembling a receptor heterotetramer composed of two T beta RI:T beta RII heterodimers. To investigate whether the two heterodimers bind and signal autonomously, one of the TGF-beta protomers was substituted to block receptor binding. The substituted dimer, TGF-beta 3 WD, bound the TbRII extracellular domain and recruited the TbRI with affinities indistinguishable from TGF-beta 3, but with one-half the stoichiometry. TGF-beta 3 WD was further shown to retain one-quarter to one-half the signalling activity of TGF-beta 3 in three established assays for TGF-beta function. Single-molecule fluorescence imaging with GFP-tagged receptors demonstrated a measurable increase in the proportion of TbRI and TbRII dimers upon treatment with TGF-beta 3, but not with TGF-beta 3 WD. These results provide evidence that the two T beta RI:T beta RII heterodimers bind and signal in an autonomous manner. They further underscore how the TGF-beta s diverged from the bone morphogenetic proteins, the ancestral ligands of the TGF-beta superfamily that signal through a RI:RII:RII heterotrimer. The EMBO Journal (2011) 30, 1263-1276. doi: 10.1038/emboj.2011.54; Published online 18 March 2011
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000290305200011
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/71491]
专题	中国科学院化学研究所
通讯作者	Hinck, Andrew P.
作者单位	1.Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA 2.Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada 3.Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad De Mexico, Mexico 4.Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Key Lab Mol Nanostruct & Nanotechnol, Beijing 100080, Peoples R China 5.Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA 6.Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada
推荐引用方式 GB/T 7714	Huang, Tao,David, Laurent,Mendoza, Valentin,et al. TGF-beta signalling is mediated by two autonomously functioning T beta RI:T beta RII pairs[J]. EMBO JOURNAL,2011,30(7):1263-1276.
APA	Huang, Tao.,David, Laurent.,Mendoza, Valentin.,Yang, Yong.,Villarreal, Maria.,...&Hinck, Andrew P..(2011).TGF-beta signalling is mediated by two autonomously functioning T beta RI:T beta RII pairs.EMBO JOURNAL,30(7),1263-1276.
MLA	Huang, Tao,et al."TGF-beta signalling is mediated by two autonomously functioning T beta RI:T beta RII pairs".EMBO JOURNAL 30.7(2011):1263-1276.