Research Papers:

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

Young Soo Park _, Dong Joon Kim, Han Koo, Se Hwan Jang, Yeon-Mi You, Jung Hee Cho, Suk-Jin Yang, Eun Sil Yu, Yuri Jung, Dong Chul Lee, Jung-Ae Kim, Zee-Yong Park, Kyung Chan Park and Young Il Yeom

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Oncotarget. 2016; 7:48155-48167. https://doi.org/10.18632/oncotarget.10179

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Young Soo Park1,5, Dong Joon Kim2, Han Koo2,5, Se Hwan Jang3, Yeon-Mi You1,5, Jung Hee Cho2, Suk-Jin Yang1, Eun Sil Yu4, Yuri Jung2, Dong Chul Lee1, Jung-Ae Kim2,5, Zee-Yong Park3, Kyung Chan Park2, Young Il Yeom1,5

1Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea

2Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea

3School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea

4Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea

5Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea

Correspondence to:

Kyung Chan Park, email: [email protected]

Young Il Yeom, email: [email protected]

Zee-Yong Park, email: [email protected]

Keywords: PKM2, AKT, IGF-1, phosphorylation of PKM2, STAT5

Received: September 30, 2015    Accepted: June 04, 2016    Published: June 20, 2016


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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