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

Authors

Rithwik Ramachandran, University of Calgary
Azza Eissa, University of Toronto
Koichiro Mihara, University of Calgary
Katerina Oikonomopoulou, University of Pennsylvania Perelman School of Medicine
Mahmoud Saifeddine, University of Calgary
Bernard Renaux, University of Calgary
Eleftherios Diamandis, University of Toronto
Morley D. Hollenberg, University of Calgary

Document Type

Conference Proceeding

Publication Date

4-1-2012

Journal

Biological Chemistry

Volume

393

Issue

5

First Page

421

Last Page

427

URL with Digital Object Identifier

10.1515/hsz-2011-0251

Abstract

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 analy sed processing by KLK8 vs. KLK14 of synthetic human and rat PAR2-derived sequences representing the cleavageactivation 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. © 2012 by Walter de Gruyter · Berlin · Boston.