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Axial patterning by a prohormone converting enzyme, PC6

激素原转换酶 PC6 的轴向图案

基本信息

批准号：
20570143
负责人：
NISHIMATSU Shin-Ichiro
金额：
$ 3.16万
依托单位：
Kawasaki Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

PC6 is a member of the Furin protease family and cleaves prepro-hormones and growth factors into mature proteins. Here we show that PC6 cleaves preproBMP-3b and that it is involved in the axial patterning of vertebrate embryos. Xenopus BMP-3b is expressed in the posterior neural and prechordal plates. However, injected BMP-3b induces anterior markers, and leads to secondary head formation. Since the anteriorizing activity is due to incomplete processing of the BMP-3b precursor, we anticipated that Xenopus BMP-3b protein is cleaved in the posterior neural plate. To address this notion, we examined a protease that can cleave the BMP-3b precursor, and which is expressed in the posterior-neural plate. Like many peptide hormones and growth factors, the BMP-3b-processing enzyme appeared to be tolloid-related or a furin. When injected in combination with BMP-3b, PC6 suppressed secondary head formation triggered by BMP-3b. Western blotting showed that PC6 effectively cleaved the BMP-3b precursor. An inactive PC6 that converted the amino acid of the active center into Phe from Ser, lost these activities. We also confirmed that Xenopus PC6 expression is similar to xBMP-3b, and graded from posterior to anterior. At present, we have been investigating whether the reaction of PC6 and BMP-3b is also conserved in mouse embryos. Our results suggest that the biosynthesis of BMP proteins is related to posterior-ventral patterning and tail formation, whereas abolishing BMP signaling is key to anterior-dorsal patterning and head formation.

PC6是Furin蛋白水解酶家族的一员，将前激素和生长因子裂解成成熟的蛋白质。在这里，我们表明PC6裂解前BMP-3b，并参与脊椎动物胚胎的轴向模式。非洲爪哇的BMP-3b表达于后神经板和脊索板。然而，注射BMP-3b会诱导前部标志，并导致二次头部形成。由于前化活性是由于BMP-3b前体的不完全加工所致，我们推测非洲爪哇BMP-3b蛋白在后神经板中被切割。为了解决这一概念，我们研究了一种可以裂解BMP-3b前体的蛋白酶，它在后神经板中表达。像许多多肽激素和生长因子一样，BMP-3b处理酶似乎与类固醇或呋喃有关。当与BMP-3b联合注射时，PC6抑制由BMP-3b触发的二次头部形成。Western blotting显示PC6能有效切割BMP-3b前体。将活性中心的氨基酸从丝氨酸转化为苯丙氨酸的无活性PC6失去了这些活性。我们还证实了非洲爪哇PC6的表达类似于xBMP-3b，并且从后到前递增。目前，我们一直在研究PC6和BMP-3b的反应是否在小鼠胚胎中也是保守的。我们的结果表明，BMP蛋白的生物合成与后腹构型和尾部形成有关，而取消BMP信号是前背部构型和头部形成的关键。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

VegT, eFGF and Xbra cause overall posteriorization while Xwnt8 causes eye‐level restricted posteriorization in synergy with chordin in early Xenopus development

VegT、eFGF 和 Xbra 导致整体后化，而 Xwnt8 在爪蟾早期发育中与 Chordin 协同作用，导致眼睛水平受限后化

DOI：
10.1111/j.1440-169x.2008.01014.x
发表时间：
2008
期刊：
Development
影响因子：
4.6
作者：
Hidefumi Fujii;M. Sakai;S. Nishimatsu;T. Nohno;M. Mochii;H. Orii;Kenji Watanabe
通讯作者：
Kenji Watanabe

Muscle mass regulation by myostatin-signaling related molecules.

肌生长抑制素信号相关分子的肌肉质量调节。