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GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis
G-protein coupled receptor kinase 2 (GRK2; ADRBK1, BARK1) is most known as a regulator of G-protein coupled receptors. However, GRK2 also has other functions. Medulloblastomas are the most common malignant brain cancers in children. GRK2 has not been implicated in medulloblastoma biology. Here we re...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761358/ https://www.ncbi.nlm.nih.gov/pubmed/31554835 http://dx.doi.org/10.1038/s41598-019-50157-5 |
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author | Pathania, Anup S. Ren, Xiuhai Mahdi, Min Y. Shackleford, Gregory M. Erdreich-Epstein, Anat |
author_facet | Pathania, Anup S. Ren, Xiuhai Mahdi, Min Y. Shackleford, Gregory M. Erdreich-Epstein, Anat |
author_sort | Pathania, Anup S. |
collection | PubMed |
description | G-protein coupled receptor kinase 2 (GRK2; ADRBK1, BARK1) is most known as a regulator of G-protein coupled receptors. However, GRK2 also has other functions. Medulloblastomas are the most common malignant brain cancers in children. GRK2 has not been implicated in medulloblastoma biology. Here we report that GRK2 knockdown slowed cell growth, diminished proliferation, and enhanced cisplatin- and etoposide-induced apoptosis in medulloblastoma cell lines UW228-2 and Daoy. Reciprocally, GRK2 overexpression attenuated apoptosis induced by these chemotherapy drugs. Cisplatin and etoposide increased phosphorylation of AKT (S473) and GRK2 knockdown mitigated this increase. Cisplatin and etoposide attenuated ERK phosphorylation, but GRK2 knockdown did not alter this effect. Wildtype GRK2 reversed the increase in cisplatin- and etoposide-induced apoptosis caused by GRK2 knockdown. GRK2-K220R (kinase dead) and GRK2-S670A (unphosphorylated, constitutively active) conferred protection from cisplatin that was similar to wildtype GRK2, suggesting that this protection may be mediated though a kinase-independent activity of GRK2. These data demonstrate that GRK2 contributes to proliferation and survival of these medulloblastoma cell lines and to their protection from cisplatin- and etoposide-induced apoptosis. |
format | Online Article Text |
id | pubmed-6761358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67613582019-10-02 GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis Pathania, Anup S. Ren, Xiuhai Mahdi, Min Y. Shackleford, Gregory M. Erdreich-Epstein, Anat Sci Rep Article G-protein coupled receptor kinase 2 (GRK2; ADRBK1, BARK1) is most known as a regulator of G-protein coupled receptors. However, GRK2 also has other functions. Medulloblastomas are the most common malignant brain cancers in children. GRK2 has not been implicated in medulloblastoma biology. Here we report that GRK2 knockdown slowed cell growth, diminished proliferation, and enhanced cisplatin- and etoposide-induced apoptosis in medulloblastoma cell lines UW228-2 and Daoy. Reciprocally, GRK2 overexpression attenuated apoptosis induced by these chemotherapy drugs. Cisplatin and etoposide increased phosphorylation of AKT (S473) and GRK2 knockdown mitigated this increase. Cisplatin and etoposide attenuated ERK phosphorylation, but GRK2 knockdown did not alter this effect. Wildtype GRK2 reversed the increase in cisplatin- and etoposide-induced apoptosis caused by GRK2 knockdown. GRK2-K220R (kinase dead) and GRK2-S670A (unphosphorylated, constitutively active) conferred protection from cisplatin that was similar to wildtype GRK2, suggesting that this protection may be mediated though a kinase-independent activity of GRK2. These data demonstrate that GRK2 contributes to proliferation and survival of these medulloblastoma cell lines and to their protection from cisplatin- and etoposide-induced apoptosis. Nature Publishing Group UK 2019-09-25 /pmc/articles/PMC6761358/ /pubmed/31554835 http://dx.doi.org/10.1038/s41598-019-50157-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pathania, Anup S. Ren, Xiuhai Mahdi, Min Y. Shackleford, Gregory M. Erdreich-Epstein, Anat GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title | GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title_full | GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title_fullStr | GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title_full_unstemmed | GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title_short | GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
title_sort | grk2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761358/ https://www.ncbi.nlm.nih.gov/pubmed/31554835 http://dx.doi.org/10.1038/s41598-019-50157-5 |
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