Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation
Histamine and H2 agonists transiently induce an important cAMP response in promonocytic U-937 cells but fail to induce monocytic differentiation because of a rapid receptor desensitization mediated by G protein-coupled receptor kinases (GRKs). The aims of the present study were to investigate the pa...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_0026895X_v62_n6_p1506_Fernandez |
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todo:paper_0026895X_v62_n6_p1506_Fernandez2023-10-03T14:37:12Z Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation Fernández, N. Monczor, F. Lemos, B. Notcovich, C. Baldi, A. Davio, C. Shayo, C. complement component C5a receptor complementary DNA cyclic AMP G protein coupled receptor kinase 2 histamine H2 receptor histamine H2 receptor agonist protein c fos animal cell article cell cloning cell differentiation cell maturation cell strain U937 controlled study gene expression gene technology genetic transfection human human cell monocyte nonhuman priority journal receptor down regulation signal transduction beta-Adrenergic Receptor Kinase Cell Aging Cyclic AMP Cyclic AMP-Dependent Protein Kinases DNA, Antisense Histamine Agonists Humans Monocytes Receptors, Histamine H2 U937 Cells Histamine and H2 agonists transiently induce an important cAMP response in promonocytic U-937 cells but fail to induce monocytic differentiation because of a rapid receptor desensitization mediated by G protein-coupled receptor kinases (GRKs). The aims of the present study were to investigate the participation of GRK2 in the desensitization mechanism of the H2 receptor in U-937 cells by reducing GRK2 levels through antisense technology and to evaluate the differentiating capacity of cells expressing lower GRK2 level, stimulated by H2 agonists. By stable U-937 cell transfection with a GRK2-antisense cDNA, we obtained D5 and A2 cell clones exhibiting a reduction in GRK2 expression and an H3 clone with no significant difference in GRK2 expression from control cells. The cAMP response induced by the H2 agonist in D5 and A2 but not in H3 cells was higher than in U-937 and persisted for a longer period of time, although the number of H2 receptors in D5 and A2 cells was lower than in U-937. Furthermore, D5 and A2 cells treated with H2 agonist showed patterns of c-Fos and CD88 expression consistent with monocytic differentiated cells. Overall, these results indicate a direct correlation between the expression of GRK2 and the desensitization of natively expressed H2 receptors in U-937 cells, suggesting that GRK2 plays a major role in the regulation of these receptors' response. In turn, desensitization process is a key component of H2 receptor signaling, determining the differentiation capability of promonocytic cells. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0026895X_v62_n6_p1506_Fernandez |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
complement component C5a receptor complementary DNA cyclic AMP G protein coupled receptor kinase 2 histamine H2 receptor histamine H2 receptor agonist protein c fos animal cell article cell cloning cell differentiation cell maturation cell strain U937 controlled study gene expression gene technology genetic transfection human human cell monocyte nonhuman priority journal receptor down regulation signal transduction beta-Adrenergic Receptor Kinase Cell Aging Cyclic AMP Cyclic AMP-Dependent Protein Kinases DNA, Antisense Histamine Agonists Humans Monocytes Receptors, Histamine H2 U937 Cells |
| spellingShingle |
complement component C5a receptor complementary DNA cyclic AMP G protein coupled receptor kinase 2 histamine H2 receptor histamine H2 receptor agonist protein c fos animal cell article cell cloning cell differentiation cell maturation cell strain U937 controlled study gene expression gene technology genetic transfection human human cell monocyte nonhuman priority journal receptor down regulation signal transduction beta-Adrenergic Receptor Kinase Cell Aging Cyclic AMP Cyclic AMP-Dependent Protein Kinases DNA, Antisense Histamine Agonists Humans Monocytes Receptors, Histamine H2 U937 Cells Fernández, N. Monczor, F. Lemos, B. Notcovich, C. Baldi, A. Davio, C. Shayo, C. Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| topic_facet |
complement component C5a receptor complementary DNA cyclic AMP G protein coupled receptor kinase 2 histamine H2 receptor histamine H2 receptor agonist protein c fos animal cell article cell cloning cell differentiation cell maturation cell strain U937 controlled study gene expression gene technology genetic transfection human human cell monocyte nonhuman priority journal receptor down regulation signal transduction beta-Adrenergic Receptor Kinase Cell Aging Cyclic AMP Cyclic AMP-Dependent Protein Kinases DNA, Antisense Histamine Agonists Humans Monocytes Receptors, Histamine H2 U937 Cells |
| description |
Histamine and H2 agonists transiently induce an important cAMP response in promonocytic U-937 cells but fail to induce monocytic differentiation because of a rapid receptor desensitization mediated by G protein-coupled receptor kinases (GRKs). The aims of the present study were to investigate the participation of GRK2 in the desensitization mechanism of the H2 receptor in U-937 cells by reducing GRK2 levels through antisense technology and to evaluate the differentiating capacity of cells expressing lower GRK2 level, stimulated by H2 agonists. By stable U-937 cell transfection with a GRK2-antisense cDNA, we obtained D5 and A2 cell clones exhibiting a reduction in GRK2 expression and an H3 clone with no significant difference in GRK2 expression from control cells. The cAMP response induced by the H2 agonist in D5 and A2 but not in H3 cells was higher than in U-937 and persisted for a longer period of time, although the number of H2 receptors in D5 and A2 cells was lower than in U-937. Furthermore, D5 and A2 cells treated with H2 agonist showed patterns of c-Fos and CD88 expression consistent with monocytic differentiated cells. Overall, these results indicate a direct correlation between the expression of GRK2 and the desensitization of natively expressed H2 receptors in U-937 cells, suggesting that GRK2 plays a major role in the regulation of these receptors' response. In turn, desensitization process is a key component of H2 receptor signaling, determining the differentiation capability of promonocytic cells. |
| format |
JOUR |
| author |
Fernández, N. Monczor, F. Lemos, B. Notcovich, C. Baldi, A. Davio, C. Shayo, C. |
| author_facet |
Fernández, N. Monczor, F. Lemos, B. Notcovich, C. Baldi, A. Davio, C. Shayo, C. |
| author_sort |
Fernández, N. |
| title |
Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| title_short |
Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| title_full |
Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| title_fullStr |
Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| title_full_unstemmed |
Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation |
| title_sort |
reduction of g protein-coupled receptor kinase 2 expression in u-937 cells attenuates h2 histamine receptor desensitization and induces cell maturation |
| url |
http://hdl.handle.net/20.500.12110/paper_0026895X_v62_n6_p1506_Fernandez |
| work_keys_str_mv |
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