Melatonin receptor type 1 signals to extracellular signal-regulated kinase 1 and 2 via Gi and Gs dually coupled pathways in HEK-293 cells
| Autor: | Ying Shi, Xiaobai He, Xiaopan Chen, Jiajie Shao, Linjie Chen, Naiming Zhou, Xiangru Lai, Yaping Zhang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Gs alpha subunit Biology GTP-Binding Protein alpha Subunits Gi-Go Pertussis toxin Biochemistry Melatonin receptor Receptors G-Protein-Coupled Melatonin Pineal gland Phosphatidylinositol 3-Kinases Internal medicine medicine Cyclic AMP GTP-Binding Protein alpha Subunits Gs Humans Phosphorylation Receptor Protein kinase C Protein Kinase C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Kinase Receptor Melatonin MT2 Receptor Melatonin MT1 Cell biology medicine.anatomical_structure Endocrinology HEK293 Cells medicine.drug Signal Transduction |
| Zdroj: | Biochemistry. 53(17) |
| ISSN: | 1520-4995 |
| Popis: | The pineal gland hormone melatonin exerts its regulatory roles in a variety of physiological and pathological responses through two G protein-coupled receptors, melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2), which have been recognized as promising targets in the treatment of a number of human diseases and disorders. The MT1 receptor was identified nearly 20 years ago; however, the molecular mechanisms by which MT1-mediated signaling affects physiology remain to be further elucidated. In this study, using HEK293 cells stably expressing the human MT1 receptor, melatonin induced a concentration-dependent activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). The melatonin-mediated phosphorylation of ERK1/2 at later time points (≥5 min) was strongly suppressed by pretreatment with pertussis toxin, but only a slight, if any, inhibition of ERK1/2 activation at early time points (≤2 min) was detected. Further experiments demonstrated that the Gβγ subunit, phosphoinositide 3-kinase, and calcium-insensitive protein kinase C were involved in the MT1-mediated activation of ERK1/2 at later time points (≥5 min). Moreover, results derived from cAMP assays combined with a MT1 mutant indicated that the human MT1 receptor could also couple to Gs protein, stimulating intracellular cAMP formation, and that the MT1-induced activation of ERK1/2 at early time points (≤2 min) was mediated by the Gs/cAMP/PKA cascade. Our findings may provide new insights into the pharmacological effects and physiological functions modulated by the MT1-mediated activation of ERK1/2. |
| Databáze: | OpenAIRE |
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