Leibniz Institute for Age Research - Fritz Lipmann Institute, Herrlich Laboratory, Beutenbergstr. 11, 07745 Jena, Germany.
Trends Biochem Sci. 2013 Mar;38(3):111-20. doi: 10.1016/j.tibs.2012.12.002. Epub 2013 Jan 5.
Many life-essential molecules such as growth factors, cytokines, ectoenzymes, and decoy receptors are produced by ectodomain cleavage of transmembrane precursor molecules. Not surprisingly, misregulation of such essential functions is linked to numerous diseases. Ectodomain cleavage is the function of transmembrane ADAMs (a disintegrin and metalloprotease) and other membrane-bound metalloproteases, which have an extracellular catalytic domain. Almost all work on ectodomain cleavage regulation has focused on the control of enzyme activity determined by substrate cleavage as surrogate. However, the number of substrates far exceeds the number of enzymes. Specificity can therefore not be achieved by solely modulating enzyme activity. Here, we argue that specific regulatory pathways must exist to control the availability and susceptibility of substrates.
许多生命必需的分子，如生长因子、细胞因子、外切酶和诱饵受体，都是通过跨膜前体分子的胞外域切割产生的。毫不奇怪，这种必需功能的失调与许多疾病有关。胞外域切割是跨膜 ADAMs（解整合素和金属蛋白酶）和其他膜结合金属蛋白酶的功能，它们具有细胞外催化结构域。几乎所有关于胞外域切割调节的工作都集中在通过作为替代物的底物切割来控制酶活性的控制上。然而，底物的数量远远超过了酶的数量。因此，仅通过调节酶活性是无法实现特异性的。在这里，我们认为必须存在特定的调节途径来控制底物的可用性和易感性。
