A proteolytic cascade of kallikreins in the stratum corneum
A proteolytic cascade of kallikreins in the stratum corneum
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DOI：
10.1111/j.0022-202x.2004.23547.x
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发表时间：
2005-01-01
影响因子：
6.5
通讯作者：
Egelrud, T
中科院分区：
文献类型：
--
作者：
Brattsand, M;Stefansson, K;Egelrud, T
属于激肽释放酶组的丝氨酸蛋白酶可能在脱屑中起核心作用。我们已经鉴定了角质层中催化活性形式的人激肽释放酶5、7和14（hK 5、hK 7、hK 14）。所有三种酶都是作为无活性的前体产生的。在这项工作中，我们制备了重组酶和酶前体，并表征了hK 5和hK 14的催化性质。对于肽底物，hK 5和hK 14均显示胰蛋白酶样特异性和碱性pH最适。对于所测试的底物，就最大催化速率以及催化效率而言，hK 14优于hK 5上级。hK 5在pH 5-7的反应中能激活pro-hK 7，而hK 14则不能。hK 5可以激活其自身的前体以及pro-hK 14。这与hK 14相反，hK 14可以激活pro-hK 5，但不能激活其自身的前体。在中性或弱碱性pH下，通过自活化或通过hK 14的pro-hK 5的活化以最大速率发生，而通过hK 5的pro-hK 14的活化在pH 6-7下最佳。我们的结论是，研究的酶可能是角质层中的蛋白酶级联的一部分，并且观察到的pH效应可能具有生理相关性。
Serine proteases belonging to the kallikrein group may play a central role in desquamation. We have identified human kallikreins 5, 7, and 14 (hK5, hK7, hK14) in catalytically active form in stratum corneum. All three enzymes are produced as inactive precursors. In this work, we prepared recombinant enzymes and enzyme precursors and characterized the catalytic properties of hK5 and hK14. With peptide substrates hK5 and hK14 both showed trypsin-like specificity and alkaline pH-optima. For the substrates tested, hK14 was superior to hK5 as regards maximum catalytic rate as well as catalytic efficiency. hK5, but not hK14, could activate pro-hK7 in a reaction which was optimal at pH 5-7. hK5 could activate its own precursor as well as pro-hK14. This was in contrast to hK14, which could activate pro-hK5 but not its own precursor. The activation of pro-hK5 either by auto-activation or by hK14 occurred at maximum rate at neutral or weakly alkaline pH, whereas activation of pro-hK14 by hK5 was optimal at pH 6-7. We conclude that the enzymes studied may be part of a protease cascade in the stratum corneum, and that the observed pH effects may have physiological relevance.