Hopkins Delana R, Keles Sunduz, Greenspan Daniel S
Program in Molecular and Cellular Pharmacology, University of Wisconsin, Madison, WI 53706, USA.
Matrix Biol. 2007 Sep;26(7):508-23. doi: 10.1016/j.matbio.2007.05.004. Epub 2007 May 18.
A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the activity necessary for proteolytic removal of the C-propeptides of procollagens I-III: precursors of the major fibrillar collagens. Subsequent studies have shown BMP1 to be the prototype of a small group of extracellular metalloproteinases that play manifold roles in regulating formation of the extracellular matrix (ECM). Soon after initial cloning of BMP1, genetic studies showed the related Drosophila proteinase Tolloid (TLD) to be necessary for the formation of the dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD-like proteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of transforming growth factor beta (TGFbeta)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic (arthropods). More recently, it has become apparent that the BMP1/TLD-like proteinases are activators of a broader subset of the TGFbeta superfamily of proteins, with implications that these proteinases may be key in orchestrating the formation of ECM with growth factor activation and BMP signaling in morphogenetic processes.
十年前，骨形态发生蛋白1（BMP1）被证明具有蛋白水解去除I-III型前胶原C-前肽（主要纤维状胶原的前体）所需的活性。随后的研究表明，BMP1是一小类细胞外金属蛋白酶的原型，这些酶在调节细胞外基质（ECM）形成中发挥多种作用。在BMP1最初克隆后不久，遗传学研究表明，相关的果蝇蛋白酶Tolloid（TLD）在早期胚胎发育中对背腹轴的形成是必需的。现在很清楚，从果蝇到人类的物种中保守的BMP1/TLD样蛋白酶，通过激活转化生长因子β（TGFβ）样蛋白BMP2、BMP4（脊椎动物）和dpp（节肢动物）在背腹模式形成中起作用。最近，很明显BMP1/TLD样蛋白酶是TGFβ超家族更广泛蛋白质子集的激活剂，这意味着这些蛋白酶可能是在形态发生过程中通过生长因子激活和BMP信号传导协调ECM形成的关键。
