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AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth

Pyruvate kinase muscle type 2 (PKM2) exhibits post-translational modifications in response to various signals from the tumor microenvironment. Insulin-like growth factor 1 (IGF-1) is a crucial signal in the tumor microenvironment that promotes cell growth and survival in many human cancers. Herein,...

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Autores principales: Park, Young Soo, Kim, Dong Joon, Koo, Han, Jang, Se Hwan, You, Yeon-Mi, Cho, Jung Hee, Yang, Suk-Jin, Yu, Eun Sil, Jung, Yuri, Lee, Dong Chul, Kim, Jung-Ae, Park, Zee-Yong, Park, Kyung Chan, Yeom, Young Il
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217008/
https://www.ncbi.nlm.nih.gov/pubmed/27340866
http://dx.doi.org/10.18632/oncotarget.10179
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author Park, Young Soo
Kim, Dong Joon
Koo, Han
Jang, Se Hwan
You, Yeon-Mi
Cho, Jung Hee
Yang, Suk-Jin
Yu, Eun Sil
Jung, Yuri
Lee, Dong Chul
Kim, Jung-Ae
Park, Zee-Yong
Park, Kyung Chan
Yeom, Young Il
author_facet Park, Young Soo
Kim, Dong Joon
Koo, Han
Jang, Se Hwan
You, Yeon-Mi
Cho, Jung Hee
Yang, Suk-Jin
Yu, Eun Sil
Jung, Yuri
Lee, Dong Chul
Kim, Jung-Ae
Park, Zee-Yong
Park, Kyung Chan
Yeom, Young Il
author_sort Park, Young Soo
collection PubMed
description Pyruvate kinase muscle type 2 (PKM2) exhibits post-translational modifications in response to various signals from the tumor microenvironment. Insulin-like growth factor 1 (IGF-1) is a crucial signal in the tumor microenvironment that promotes cell growth and survival in many human cancers. Herein, we report that AKT directly interacts with PKM2 and phosphorylates it at Ser-202, which is essential for the nuclear translocation of PKM2 protein under stimulation of IGF-1. In the nucleus, PKM2 binds to STAT5A and induces IGF-1-stimulated cyclin D1 expression, suggesting that PKM2 acts as an important factor inducing STAT5A activation under IGF-1 signaling. Concordantly, overexpression of STAT5A in cells deficient in PKM2 expression failed to restore IGF-induced growth, whereas reconstitution of PKM2 in PKM2 knockdown cells restored the IGF-induced growth capacity. Our findings suggest a novel role of PKM2 in promoting the growth of cancers with dysregulated IGF/phosphoinositide 3-kinase/AKT signaling.
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spelling pubmed-52170082017-01-17 AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth Park, Young Soo Kim, Dong Joon Koo, Han Jang, Se Hwan You, Yeon-Mi Cho, Jung Hee Yang, Suk-Jin Yu, Eun Sil Jung, Yuri Lee, Dong Chul Kim, Jung-Ae Park, Zee-Yong Park, Kyung Chan Yeom, Young Il Oncotarget Research Paper Pyruvate kinase muscle type 2 (PKM2) exhibits post-translational modifications in response to various signals from the tumor microenvironment. Insulin-like growth factor 1 (IGF-1) is a crucial signal in the tumor microenvironment that promotes cell growth and survival in many human cancers. Herein, we report that AKT directly interacts with PKM2 and phosphorylates it at Ser-202, which is essential for the nuclear translocation of PKM2 protein under stimulation of IGF-1. In the nucleus, PKM2 binds to STAT5A and induces IGF-1-stimulated cyclin D1 expression, suggesting that PKM2 acts as an important factor inducing STAT5A activation under IGF-1 signaling. Concordantly, overexpression of STAT5A in cells deficient in PKM2 expression failed to restore IGF-induced growth, whereas reconstitution of PKM2 in PKM2 knockdown cells restored the IGF-induced growth capacity. Our findings suggest a novel role of PKM2 in promoting the growth of cancers with dysregulated IGF/phosphoinositide 3-kinase/AKT signaling. Impact Journals LLC 2016-06-20 /pmc/articles/PMC5217008/ /pubmed/27340866 http://dx.doi.org/10.18632/oncotarget.10179 Text en Copyright: © 2016 Park et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Park, Young Soo
Kim, Dong Joon
Koo, Han
Jang, Se Hwan
You, Yeon-Mi
Cho, Jung Hee
Yang, Suk-Jin
Yu, Eun Sil
Jung, Yuri
Lee, Dong Chul
Kim, Jung-Ae
Park, Zee-Yong
Park, Kyung Chan
Yeom, Young Il
AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title_full AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title_fullStr AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title_full_unstemmed AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title_short AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth
title_sort akt-induced pkm2 phosphorylation signals for igf-1-stimulated cancer cell growth
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217008/
https://www.ncbi.nlm.nih.gov/pubmed/27340866
http://dx.doi.org/10.18632/oncotarget.10179
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