title: Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14.
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 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Faculty of Medicine, AB, Canada.
authors.forename: Rithwik
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Azza
authors.initials: A
authors.lastname: Eissa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Mihara
authors.forename: Katerina
authors.initials: K
authors.lastname: Oikonomopoulou
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Saifeddine
authors.forename: Bernard
authors.initials: B
authors.lastname: Renaux
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Diamandis
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D044464:Receptor, PAR-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D044464:Receptor, PAR-2; C425336:KLK14 protein, human; C094799:KLK8 protein, human; D007610:Kallikreins