Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14

被引：18
|
作者：
Ramachandran, Rithwik [1 ]
Eissa, Azza [2 ]
Mihara, Koichiro [1 ]
Oikonomopoulou, Katerina [3 ]
Saifeddine, Mahmoud [1 ]
Renaux, Bernard [1 ]
Diamandis, Eleftherios [2 ]
Hollenberg, Morley D. [1 ]
机构：
[1] Univ Calgary, Fac Med, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada
[2] Univ Toronto, Mt Sinai Hosp, Joseph & Wolf Lebovic Ctr, Dept Lab Med & Pathobiol, Toronto, ON M5T 3L9, Canada
[3] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
来源：
BIOLOGICAL CHEMISTRY | 2012年 / 393卷 / 05期
基金：
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词：
beta-arrestin; KLK8; KLK14; protease-activated receptors; proteinase-activated receptors; NETHERTON-SYNDROME; FUNCTIONAL SELECTIVITY; THROMBIN RECEPTORS; SERINE-PROTEASE; EXPRESSION; CANCER; INFLAMMATION; SKIN;
D O I：
10.1515/hsz-2011-0251
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We compared signalling pathways such as calcium transients, MAPK activation, beta-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 PAR I. Thus, KLK8 and KLK14 can signal differentially via the PARs to affect tissue function.
引用
收藏
页码：421 / 427
页数：7
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