title: Cellular signalling of cysteinyl leukotriene type 1 receptor variants CysLT₁-G300S and CysLT₁-I206S.
abstract: Cysteinyl-leukotrienes are pro-inflammatory lipid mediators, involved in allergic asthma, that bind the G-protein-coupled receptors CysLT1, CysLT2 and GPR99. A polymorphism in one of these receptors, CysLT1-G300S was strongly associated with atopy, whereas the CysLT1-I206S polymorphism was not. In the present work, our aim was to characterize these two variants by studying their cellular signalling. Cell surface expression of mutant receptors in transfected HEK-293 cells was comparable to that of the wild-type receptor. Compared to CysLT1-WT, production of inositol phosphates as well as IL-8 and IL-13 promoter transactivation in response to either LTD4 or LTC4 was significantly increased in CysLT1-G300S-transfected cells. Moreover, LTD4-induced phosphorylation of the signalling effector Erk, but not p38, p65 or c-Jun was higher in CysLT1-G300S-transfected cells. On the other hand, the variant CysLT1-I206S did not show a significant difference in its signal transduction compared to the wild-type receptor. Taken together, our results indicate that the variant CysLT1-G300S can induce a greater signal than the CysLT1-WT receptor, a feature that may be relevant to its association with atopy.
authors: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors: Louiza
authors: L
authors: Yaddaden
authors: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors: Steeve
authors: S
authors: Véronneau
authors: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors: Miles D
authors: MD
authors: Thompson
authors: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors: Marek
authors: M
authors: Rola-Pleszczynski
authors: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4. Electronic address: jana.stankova@usherbrooke.ca.
authors: Jana
authors: J
authors: Stankova
mesh_terms: D015153:Blotting, Western; D057809:HEK293 Cells; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor
keywords: Atopy; CysLT(1); Cysteinyl-leukotriene; Signalling; Variant