Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor
| Autor: | Kamonchanok Sansuk, Paul L. Chazot, Remko A. Bakker, Richard M. van Rijn, Rob Leurs, Yongjun Qin, Fiona C. Shenton, Michel Dy, Obbe P. Zuiderveld, André van Marle, Cornelis P. Tensen, Ellen Langemeijer, Martine J. Smit, Herman D. Lim |
|---|---|
| Přispěvatelé: | Slama, Catherine, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Medicinal chemistry, Molecular and Computational Toxicology |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Gene isoform
Molecular Sequence Data Population HL-60 Cells Biology Biochemistry Receptors G-Protein-Coupled Histamine receptor chemistry.chemical_compound SDG 3 - Good Health and Well-being Chlorocebus aethiops Animals Humans Protein Isoforms splice Amino Acid Sequence Histamine H4 receptor Cloning Molecular Receptor education Molecular Biology Cells Cultured ComputingMilieux_MISCELLANEOUS Receptors Histamine H4 G protein-coupled receptor education.field_of_study Genetic Variation Cell Biology Fetal Blood Molecular biology chemistry COS Cells Receptors Histamine Histamine |
| Zdroj: | van Rijn, R, van Marle, A, Chazot, P L, Langemeijer, E V, Qin, Y, Shenton, F C, Lim, H D, Zuiderveld, O P, Sansuk, K, Dy, M, Smit, M J, Tensen, C P, Bakker, R A & Leurs, R 2008, ' Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor ', Biochemical Journal, vol. 414, no. 1, pp. 121-31 . https://doi.org/10.1042/BJ20071583 Biochemical Journal Biochemical Journal, Portland Press, 2008, 414, pp.121-131 Biochem. J. Biochem. J., 2008, 414, pp.121-131 Biochemical Journal, 414(1), 121-31. Portland Press Ltd. |
| ISSN: | 0264-6021 1470-8728 |
| DOI: | 10.1042/BJ20071583 |
| Popis: | The H(4)R (histamine H(4) receptor) is the latest identified member of the histamine receptor subfamily of GPCRs (G-protein-coupled receptors) with potential functional implications in inflammatory diseases and cancer. The H(4)R is primarily expressed in eosinophils and mast cells and has the highest homology with the H(3)R. The occurrence of at least twenty different hH(3)R (human H(3)R) isoforms led us to investigate the possible existence of H(4)R splice variants. In the present paper, we report on the cloning of the first two alternatively spliced H(4)R isoforms from CD34+ cord blood-cell-derived eosinophils and mast cells. These H(4)R splice variants are localized predominantly intracellularly when expressed recombinantly in mammalian cells. We failed to detect any ligand binding, H(4)R-ligand induced signalling or constitutive activity for these H(4)R splice variants. However, when co-expressed with full-length H(4)R [H(4)R((390)) (H(4)R isoform of 390 amino acids)], the H(4)R splice variants have a dominant negative effect on the surface expression of H(4)R((390)). We detected H(4)R((390))-H(4)R splice variant hetero-oligomers by employing both biochemical (immunoprecipitation and cell-surface labelling) and biophysical [time-resolved FRET (fluorescence resonance energy transfer)] techniques. mRNAs encoding the H(4)R splice variants were detected in various cell types and expressed at similar levels to the full-length H(4)R((390)) mRNA in, for example, pre-monocytes. We conclude that the H(4)R splice variants described here have a dominant negative effect on H(4)R((390)) functionality, as they are able to retain H(4)R((390)) intracellularly and inactivate a population of H(4)R((390)), presumably via hetero-oligomerization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|