Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14
- PMID: 22505524
- DOI: 10.1515/hsz-2011-0251
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.
Similar articles
-
Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs).Biol Chem. 2006 Jun;387(6):817-24. doi: 10.1515/BC.2006.104. Biol Chem. 2006. PMID: 16800746
-
Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases.J Invest Dermatol. 2008 Jan;128(1):18-25. doi: 10.1038/sj.jid.5700965. Epub 2007 Jul 12. J Invest Dermatol. 2008. PMID: 17625593
-
Kallikrein-related peptidase signaling in colon carcinoma cells: targeting proteinase-activated receptors.Biol Chem. 2012 Apr;393(5):413-20. doi: 10.1515/bc-2011-231. Biol Chem. 2012. PMID: 22505523
-
Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer.Biol Chem. 2008 Jun;389(6):643-51. doi: 10.1515/BC.2008.077. Biol Chem. 2008. PMID: 18627296 Review.
-
Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs).Biol Chem. 2008 Jun;389(6):653-68. doi: 10.1515/BC.2008.078. Biol Chem. 2008. PMID: 18627286 Review.
Cited by
-
Overexpression of kallikrein gene 10 is a biomarker for predicting poor prognosis in gastric cancer.World J Gastroenterol. 2013 Dec 28;19(48):9425-31. doi: 10.3748/wjg.v19.i48.9425. World J Gastroenterol. 2013. PMID: 24409072 Free PMC article.
-
Calcium Increase and Substance P Release Induced by the Neurotoxin Brevetoxin-1 in Sensory Neurons: Involvement of PAR2 Activation through Both Cathepsin S and Canonical Signaling.Cells. 2020 Dec 17;9(12):2704. doi: 10.3390/cells9122704. Cells. 2020. PMID: 33348659 Free PMC article.
-
Protease-activated receptors in kidney disease progression.Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1140-F1144. doi: 10.1152/ajprenal.00460.2016. Epub 2016 Oct 12. Am J Physiol Renal Physiol. 2016. PMID: 27733370 Free PMC article. Review.
-
Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist.PLoS One. 2014 Jun 25;9(6):e99702. doi: 10.1371/journal.pone.0099702. eCollection 2014. PLoS One. 2014. PMID: 24964046 Free PMC article.
-
Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.Biomed Res Int. 2016;2016:3130496. doi: 10.1155/2016/3130496. Epub 2016 Feb 23. Biomed Res Int. 2016. PMID: 27006943 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous
