ArticleThe Journal of biological chemistry2013
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models.Cell reports. Medicine · 2026Article
- Beef-Derived Peptides Mediated Desensitization of Bitter Taste Receptor T2R14 Through GPCR Kinase 2.Nutrients · 2026Article
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- G-protein coupled receptor kinase-2 regulates the migration of chronic lymphocytic leukaemia cells to sphingosine-1 phosphate in vitro and their trafficking in vivo.Scientific reports · 2025Article
- Exploring the potential biological function of GRK2 in colorectal cancer.Functional & integrative genomics · 2024Article
- Review
- Article
- G protein-coupled receptor kinase 5 modifies cancer cell resistance to paclitaxel.Molecular and cellular biochemistry · 2019Article
- NFkappaB is a Key Player in the Crosstalk between Inflammation and Cardiovascular Diseases.International journal of molecular sciences · 2019Review
- Discovery of Pathologic GPCR Aggregation.Frontiers in medicine · 2019Review
- Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation.Science signaling · 2018Article
- Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress.Basic research in cardiology · 2018Article
- A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics.Critical reviews in oncogenesis · 2018Review
- Sensitization of the Angiotensin II AT1 Receptor Contributes to RKIP-Induced Symptoms of Heart Failure.Frontiers in medicine · 2018Article
- Raf kinase inhibitor protein: lessons of a better way for β-adrenergic receptor activation in the heart.The Journal of physiology · 2017Review
- Exosomes Generated From iPSC-Derivatives: New Direction for Stem Cell Therapy in Human Heart Diseases.Circulation research · 2017Review
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- Dual role of GRK5 in cancer development and progression.Translational medicine @ UniSa · 2016Article
- Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) is an emerging treatment option for heart failure. Because GRK2 is also indispensable for growth and development, we analyzed the impact of GRK2 inhibition on cell growth and proliferation. Inhibition of GRK2 by the dominant-negative GRK2-K220R did not affect the proliferation of cultured cells. In contrast, upon xenograft transplantation of cells into immunodeficient mice, the dominant-negative GRK2-K220R or a GRK2-specific peptide inhibitor increased tumor mass. The enhanced tumor growth upon GRK2 inhibition was attributed to the growth-promoting MAPK pathway because dual inhibition of the GRK2 and RAF-MAPK axis by the Raf kinase inhibitor protein (RKIP) did not increase tumor mass. The MAPK cascade contributed to the cardioprotective profile of GRK2 inhibition by preventing cardiomyocyte death, whereas dual inhibition of RAF/MAPK and GRK2 by RKIP induced cardiomyocyte apoptosis, cardiac dysfunction, and signs of heart failure. Thus, cardioprotective signaling induced by GRK2 inhibition is overlapping with tumor growth promotion.
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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.