ArticleProceedings of the National Academy of Sciences of the United States of America2011
Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry.The pharmacogenomics journal · 2021Article
- Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor.Integrative biology : quantitative biosciences from nano to macro · 2021Article
- Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.Circulation research · 2019Article
- The prognostic value of ADRA1 subfamily genes in gastric carcinoma.Oncology letters · 2019Article
- Evidence for altered brain reactivity to norepinephrine in Veterans with a history of traumatic stress.Neurobiology of stress · 2018Article
- Transducin (β)-like 1 X-linked receptor 1 promotes gastric cancer progression via the ERK1/2 pathway.Oncogene · 2017Article
- Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone.Oncotarget · 2017Article
- Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway.PloS one · 2015Article
- Article
- Biased signaling in naturally occurring mutations in human melanocortin-3 receptor gene.International journal of biological sciences · 2015Article
- Squamosamide derivative FLZ protects retinal pigment epithelium cells from oxidative stress through activation of epidermal growth factor receptor (EGFR)-AKT signaling.International journal of molecular sciences · 2014Article
- Alpha1a-adrenoceptor genetic variant induces cardiomyoblast-to-fibroblast-like cell transition via distinct signaling pathways.Cellular signalling · 2014Article
- Article
- Genomic Medicine: Why Do "Similar" Patients Have Different Outcomes?Review course lectures : presented at the ... Clinical and Scientific Congress of the International Anesthesia Research Society · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
We previously identified a naturally occurring human SNP, G247R, in the third intracellular loop of the α(1a)-adrenergic receptor (α(1a)-247R) and demonstrated that constitutive expression of α(1a)-247R results in twofold increased cell proliferation compared with WT. In the present study we elucidate molecular mechanisms and signal transduction pathways responsible for increased cell proliferation unique to α(1a)-247R, but not α(1a)-WT, α(1b), or α(1d)AR subtypes. We show that elevated levels of matrix metalloproteinase-7 (MMP7) and a disintegrin and metalloproteinase-12 (ADAM12) in α(1a)-247R-expressing cells are responsible for EGF receptor (EGFR) transactivation, downstream ERK activation, and increased cell proliferation; this pathway is confirmed using MMP, EGFR, and ERK inhibitors. We demonstrate that EGFR transactivation and downstream ERK activation depends on increased shedding of heparin-binding EGF. Finally, we demonstrate that knockdown of MMP7 or β-arrestin1 by shRNAs results in attenuation of proliferation of cells expressing α(1a)-247R. Importantly, accelerated cell proliferation triggered by the α(1a)-247R is serum- and agonist-independent, providing unique evidence for constitutive active coupling to the β-arrestin1/MMP/EGFR transactivation pathway by any G protein-coupled receptor. These findings raise the possibility of a previously unexplored mechanism for sympathetically mediated human hypertension triggered by a naturally occurring human genetic variant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.