Absence of integrin-mediated TGFβ1 activation in vivo recapitulates the phenotype of TGFβ1-null mice

被引：246

作者：

Yang, Zhiwei ^{[1
]}

Mu, Zhenyu ^{[1
]}

Dabovic, Branka ^{[1
]}

Jurukovski, Vladimir ^{[1
]}

Yu, Dawen ^{[1
]}

Sung, Joanne ^{[1
]}

Xiong, Xiaozhong ^{[1
]}

Munger, John S. ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

来源：

JOURNAL OF CELL BIOLOGY | 2007年 / 176卷 / 06期

关键词：

D O I：

10.1083/jcb.200611044

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The multifunctional cytokine transforming growth factor (TGF) beta 1 is secreted in a latent complex with its processed propeptide (latency-associated peptide [LAP]). TGF beta 1 must be functionally released from this complex before it can engage TGF beta receptors. One mechanism of latent TGF beta 1 activation involves interaction of the integrins alpha v beta 6 and alpha v beta 8 with an RGD sequence in LAP; other putative latent TGF beta 1 activators include thrombospondin1, oxidants, and various proteases. To assess the contribution of RGD-binding integrins to TGF beta 1 activation in vivo, we created a mutation in Tgfb1 encoding a nonfunctional variant of the RGD sequence (RGE). Mice with this mutation (Tgfb1(RGE/RGE)) display the major features of Tgfb1(-/-) mice (vasculogenesis defects, multiorgan inflammation, and lack of Langerhans cells) despite production of normal levels of latent TGF beta 1. These. ndings indicate that RGD-binding integrins are requisite latent TGF beta 1 activators during development and in the immune system.

引用

页码：787 / 793

页数：7

共 27 条

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