UM
Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes
Kamato D.6; Thach L.5; Getachew R.6; Burch M.4; Hollenberg M.D.1; Zheng W.3; Little P.J.6; Osman N.6
2016
Source PublicationCellular Signalling
ISSN18733913 08986568
Volume28Issue:1Pages:110-119
AbstractG protein-coupled receptors (GPCR) are one of the most important targets for therapeutics due to their abundance and diversity. The G protein-coupled receptor for thrombin can transactivate protein tyrosine kinase receptors (PTKR) and we have recently established that it can also transactivate serine/threonine kinase receptors (S/TKR). A comprehensive knowledge of the signalling pathways that GPCR transactivation elicits is necessary to fully understand the implications of both GPCR activation and the impact of target drugs. Here, we demonstrate that thrombin elicits dual transactivation-dependent signalling pathways to stimulate mRNA expression of glycosaminoglycan synthesizing enzymes chondroitin 4-O-sulfotransferase 1 and chondroitin sulfate synthase 1. The PTKR mediated response involves matrix metalloproteinases and the phosphorylation of the MAP kinase Erk. The S/TKR mediated response differs markedly and involves the phosphorylation of Smad2 carboxy terminal serine residues and does not involve matrix metalloproteinases. This work shows that all of the thrombin mediated signalling to glycosaminoglycan synthesizing enzyme gene expression occurs via transactivation-dependent pathways and does not involve transactivation-independent signalling. These findings highlight the complexity of thrombin-mediated transactivation signalling and the broader implications of GPCR targeted therapeutics.
KeywordGlycosaminoglycan enzymes Smad linker region Thrombin Transactivation-dependent Transforming growth factor β
DOI10.1016/j.cellsig.2015.11.003
URLView the original
Language英語
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Cited Times [WOS]:23   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Calgary
2.Zhongshan Ophthalmic Center
3.Universidade de Macau
4.Harvard Medical School
5.University of Queensland
6.RMIT University
Recommended Citation
GB/T 7714
Kamato D.,Thach L.,Getachew R.,et al. Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes[J]. Cellular Signalling,2016,28(1):110-119.
APA Kamato D..,Thach L..,Getachew R..,Burch M..,Hollenberg M.D..,...&Osman N..(2016).Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes.Cellular Signalling,28(1),110-119.
MLA Kamato D.,et al."Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes".Cellular Signalling 28.1(2016):110-119.
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