title: AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth.
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.
authors.affiliation: Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Han
authors.initials: H
authors.lastname: Koo
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Yeon-Mi
authors.initials: YM
authors.lastname: You
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Suk-Jin
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Yu
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Lee
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.
authors.forename: Zee-Yong
authors.initials: ZY
authors.lastname: Park
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Kyung Chan
authors.initials: KC
authors.lastname: Park
authors.affiliation: Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon 34113, Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; D050799:STAT5 Transcription Factor; D013963:Thyroid Hormones; D025521:Tumor Suppressor Proteins; D000097810:Thyroid Hormone-Binding Proteins; C494092:STAT5A protein, human
keywords: AKT; IGF-1; PKM2; STAT5; phosphorylation of PKM2