Cited 39 time in
- Title
- AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth = AKT에의한 PKM2 인산화 시그널을 통한 IGF 유도 암세포 성장조절
- Author(s)
- Young Soo Park; Dong Joon Kim; Han Koo; S H Jang; Yeon Mi You; Jung Hee Cho; Suk-Jin Yang; E S Yu; Yuri Jung; Dong Chul Lee; Jung Ae Kim; Z Y Park; Kyung Chan Park; Young Il Yeom
- Bibliographic Citation
- Oncotarget, vol. 7, no. 30, pp. 48155-48167
- Publication Year
- 2016
- Abstract
- 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.
- Keyword
- AKTIGF-1Phosphorylation of PKM2PKM2STAT5
- ISSN
- 1949-2553
- Publisher
- Impact Journals
- DOI
- http://dx.doi.org/10.18632/oncotarget.10179
- Type
- Article
- Appears in Collections:
- Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
- Files in This Item:
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