Axial patterning by a prohormone converting enzyme, PC6

PC6是弗林蛋白酶家族的成员，将前激素原和生长因子切割成成熟蛋白质。在这里，我们表明，PC6切割preproBMP-3b，它是在脊椎动物胚胎的轴向图案。非洲爪蟾BMP-3b在后神经板和前索板中表达。然而，注射的BMP-3b诱导前部标记，并导致继发性头部形成。由于前化活性是由于BMP-3b前体的不完全加工，我们预期非洲爪蟾BMP-3b蛋白在后神经板中被切割。为了解决这个问题，我们研究了一种蛋白酶，可以切割BMP-3b前体，并在后神经板中表达。像许多肽激素和生长因子一样，BMP-3b加工酶似乎与tolloid相关或弗林蛋白酶。当与BMP-3b组合注射时，PC6抑制由BMP-3b触发的次级头部形成。Western blotting显示，PC6有效地切割BMP-3b前体。将活性中心的氨基酸从Ser转化为Phe的失活PC 6失去了这些活性。我们还证实了爪蟾PC6的表达与xBMP-3b相似，并且从后向前分级。目前，我们一直在研究PC 6和BMP-3b的反应是否在小鼠胚胎中也是保守的。我们的研究结果表明，BMP蛋白的生物合成与后腹图案和尾巴的形成，而废除BMP信号是前背图案和头部形成的关键。

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.