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β2-Adrenergic receptor activation mobilizes intracellular calcium via a non-canonical cAMP-independent signaling pathway
| Content Provider | Scilit |
|---|---|
| Author | Galaz-Montoya, Monica Wright, Sara J. Rodriguez, Gustavo J. Lichtarge, Olivier Wensel, Theodore G. |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry Beta adrenergic receptors (βARs) are G-protein-coupled receptors essential for physiological responses to the hormones/neurotransmitters epinephrine and norepinephrine which are found in the nervous system and throughout the body. They are the targets of numerous widely used drugs, especially in the case of the most extensively studied βAR, $β_{2}$AR, whose ligands are used for asthma and cardiovascular disease. βARs signal through $Gα_{s}$ G-proteins and via activation of adenylyl cyclase and cAMP-dependent protein kinase, but some alternative downstream pathways have also been proposed that could be important for understanding normal physiological functioning of βAR signaling and its disruption in disease. Using fluorescence-based $Ca^{2+}$ flux assays combined with pharmacology and gene knock-out methods, we discovered a previously unrecognized endogenous pathway in HEK-293 cells whereby $β_{2}$AR activation leads to robust $Ca^{2+}$ mobilization from intracellular stores via activation of phospholipase C and opening of inositol trisphosphate $(InsP_{3}$) receptors. This pathway did not involve cAMP, $Gα_{s}$, or $Gα_{i}$ or the participation of the other members of the canonical $β_{2}$AR signaling cascade and, therefore, constitutes a novel signaling mechanism for this receptor. This newly uncovered mechanism for $Ca^{2+}$ mobilization by $β_{2}$AR has broad implications for adrenergic signaling, cross-talk with other signaling pathways, and the effects of βAR-directed drugs. |
| Related Links | http://www.jbc.org/content/292/24/9967.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473248/pdf http://www.jbc.org/article/S0021925820408038/pdf |
| Ending Page | 9974 |
| Page Count | 8 |
| Starting Page | 9967 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m117.787119 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 24 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Research and Experimental Medicine G-protein-coupled Receptor (gpcr) Adrenergic Receptor Calcium Intracellular Release Cell Signaling Cyclic Amp (camp) Β2-adrenergic Receptor |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
