Department of Physiology and Pharmacology, University of Calgary, Faculty of Medicine, AB, Canada.
Biol Chem. 2012 Apr;393(5):421-7. doi: 10.1515/hsz-2011-0251.
We compared signalling pathways such as calcium transients, MAPK activation, β-arrestin interactions and receptor internalization triggered by kallikrein-related peptidases (KLKs) 8 and 14 in human and rat proteinase-activated receptor (PAR)2-expressing human embryonic kidney (HEK) and Kirsten transformed rat kidney (KNRK) cells. Further, we analysed processing by KLK8 vs. KLK14 of synthetic human and rat PAR2-derived sequences representing the cleavage-activation domain of PAR2. Our data show that like KLK14, KLK8 can unmask a PAR2 receptor-activating sequence from a peptide precursor. However, whilst KLK8, like KLK14, can signal in rat-PAR2-expressing KNRK cells, this enzyme cannot signal via human PAR2 in HEK or KNRK cells, but rather, disarms HEK PAR1. Thus, KLK8 and KLK14 can signal differentially via the PARs to affect tissue function.
我们比较了激肽释放酶相关肽酶（KLKs）8 和 14 在人蛋白水解酶激活受体（PAR）2 表达的人胚肾（HEK）和 Kirsten 转化大鼠肾（KNRK）细胞中引发的信号通路，如钙瞬变、MAPK 激活、β-arrestin 相互作用和受体内化。此外，我们分析了 KLK8 与 KLK14 对代表 PAR2 切割激活结构域的合成人源和大鼠源 PAR2 衍生序列的加工。我们的数据表明，KLK8 与 KLK14 一样，可以从肽前体中揭示 PAR2 受体激活序列。然而，尽管 KLK8 与 KLK14 一样，可以在大鼠 PAR2 表达的 KNRK 细胞中发出信号，但该酶不能通过 HEK 中的人 PAR2 发出信号，而是使 HEK PAR1 失去作用。因此，KLK8 和 KLK14 可以通过 PAR 差异信号传导影响组织功能。
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