Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases
The histamine H2 receptor (H2r) belongs to the heptahelical receptor family; upon agonist binding, members of this family activate a G protein and the downstream effector adenylyl cyclase. Like other G protein-coupled receptors, exposure of H2r to agonists produces a desensitization of the response....
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todo:paper_0026895X_v60_n5_p1049_Shayo2023-10-03T14:37:12Z Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases Shayo, C. Fernandez, N. Legnazzi, B.L. Monczor, F. Mladovan, A. Baldi, A. Davio, C. adenylate cyclase amthamine cyclic AMP cyclic AMP dependent protein kinase cyclic AMP dependent protein kinase inhibitor G protein coupled receptor G protein coupled receptor kinase G protein coupled receptor kinase 2 G protein coupled receptor kinase 5 G protein coupled receptor kinase 6 histamine histamine H2 receptor protein GRK3 protein kinase C inhibitor protein kinase inhibitor unclassified drug animal cell article controlled study DNA transfection enzyme active site enzyme inhibition enzyme kinetics enzyme mechanism enzyme regulation enzyme specificity histamine release nonhuman priority journal protein phosphorylation receptor binding receptor down regulation signal transduction transcription termination The histamine H2 receptor (H2r) belongs to the heptahelical receptor family; upon agonist binding, members of this family activate a G protein and the downstream effector adenylyl cyclase. Like other G protein-coupled receptors, exposure of H2r to agonists produces a desensitization of the response. The present study focused on the desensitization mechanism of this receptor. Using transiently transfected COS-7 cells expressing tagged-H2r, the desensitization induced by amthamine, characterized by decreased cAMP production, was studied. Results show that the receptor was rapidly desensitized with a t1/2 = 0.49 ± 0.01 min. Because of the rapid nature of H2r desensitization, receptor phosphorylation was examined as a likely mechanism for signal attenuation. H2r desensitization was not affected by protein kinases A and C (PKA and PKC) inhibitors but was remarkably reduced by Zn2+, an inhibitor of G protein-coupled receptor kinases (GRKs). Cotransfection experiments using tagged H2r and different GRKs (2, 3, 5, or 6), demonstrated that GRK2 and GRK3 were the most potent in augmenting desensitization, causing a reduction in the maximal response to amthamine and a decrease of the t1/2 for desensitization, whereas GRK5 and GRK6 did not affect the signaling. Receptor phosphorylation correlates with desensitization for each GRK studied, whereas phosphorylation that is dependent on protein kinases A and C seemed irrelevant in receptor signal termination. These results indicate that in H2r-transfected COS-7 cells, exposure to an agonist caused desensitization controlled by H2r phosphorylation via GRK2 and GRK3. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0026895X_v60_n5_p1049_Shayo |
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Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
adenylate cyclase amthamine cyclic AMP cyclic AMP dependent protein kinase cyclic AMP dependent protein kinase inhibitor G protein coupled receptor G protein coupled receptor kinase G protein coupled receptor kinase 2 G protein coupled receptor kinase 5 G protein coupled receptor kinase 6 histamine histamine H2 receptor protein GRK3 protein kinase C inhibitor protein kinase inhibitor unclassified drug animal cell article controlled study DNA transfection enzyme active site enzyme inhibition enzyme kinetics enzyme mechanism enzyme regulation enzyme specificity histamine release nonhuman priority journal protein phosphorylation receptor binding receptor down regulation signal transduction transcription termination |
| spellingShingle |
adenylate cyclase amthamine cyclic AMP cyclic AMP dependent protein kinase cyclic AMP dependent protein kinase inhibitor G protein coupled receptor G protein coupled receptor kinase G protein coupled receptor kinase 2 G protein coupled receptor kinase 5 G protein coupled receptor kinase 6 histamine histamine H2 receptor protein GRK3 protein kinase C inhibitor protein kinase inhibitor unclassified drug animal cell article controlled study DNA transfection enzyme active site enzyme inhibition enzyme kinetics enzyme mechanism enzyme regulation enzyme specificity histamine release nonhuman priority journal protein phosphorylation receptor binding receptor down regulation signal transduction transcription termination Shayo, C. Fernandez, N. Legnazzi, B.L. Monczor, F. Mladovan, A. Baldi, A. Davio, C. Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| topic_facet |
adenylate cyclase amthamine cyclic AMP cyclic AMP dependent protein kinase cyclic AMP dependent protein kinase inhibitor G protein coupled receptor G protein coupled receptor kinase G protein coupled receptor kinase 2 G protein coupled receptor kinase 5 G protein coupled receptor kinase 6 histamine histamine H2 receptor protein GRK3 protein kinase C inhibitor protein kinase inhibitor unclassified drug animal cell article controlled study DNA transfection enzyme active site enzyme inhibition enzyme kinetics enzyme mechanism enzyme regulation enzyme specificity histamine release nonhuman priority journal protein phosphorylation receptor binding receptor down regulation signal transduction transcription termination |
| description |
The histamine H2 receptor (H2r) belongs to the heptahelical receptor family; upon agonist binding, members of this family activate a G protein and the downstream effector adenylyl cyclase. Like other G protein-coupled receptors, exposure of H2r to agonists produces a desensitization of the response. The present study focused on the desensitization mechanism of this receptor. Using transiently transfected COS-7 cells expressing tagged-H2r, the desensitization induced by amthamine, characterized by decreased cAMP production, was studied. Results show that the receptor was rapidly desensitized with a t1/2 = 0.49 ± 0.01 min. Because of the rapid nature of H2r desensitization, receptor phosphorylation was examined as a likely mechanism for signal attenuation. H2r desensitization was not affected by protein kinases A and C (PKA and PKC) inhibitors but was remarkably reduced by Zn2+, an inhibitor of G protein-coupled receptor kinases (GRKs). Cotransfection experiments using tagged H2r and different GRKs (2, 3, 5, or 6), demonstrated that GRK2 and GRK3 were the most potent in augmenting desensitization, causing a reduction in the maximal response to amthamine and a decrease of the t1/2 for desensitization, whereas GRK5 and GRK6 did not affect the signaling. Receptor phosphorylation correlates with desensitization for each GRK studied, whereas phosphorylation that is dependent on protein kinases A and C seemed irrelevant in receptor signal termination. These results indicate that in H2r-transfected COS-7 cells, exposure to an agonist caused desensitization controlled by H2r phosphorylation via GRK2 and GRK3. |
| format |
JOUR |
| author |
Shayo, C. Fernandez, N. Legnazzi, B.L. Monczor, F. Mladovan, A. Baldi, A. Davio, C. |
| author_facet |
Shayo, C. Fernandez, N. Legnazzi, B.L. Monczor, F. Mladovan, A. Baldi, A. Davio, C. |
| author_sort |
Shayo, C. |
| title |
Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| title_short |
Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| title_full |
Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| title_fullStr |
Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| title_full_unstemmed |
Histamine H2 receptor desensitization: Involvement of a select array of G protein-coupled receptor kinases |
| title_sort |
histamine h2 receptor desensitization: involvement of a select array of g protein-coupled receptor kinases |
| url |
http://hdl.handle.net/20.500.12110/paper_0026895X_v60_n5_p1049_Shayo |
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