IGF1 regulates PKM2 function through Akt phosphorylation

Cell Cycle
Barbara SalaniDavide Maggi

Abstract

Pyruvate kinase M2 (PKM2) acts at the crossroad of growth and metabolism pathways in cells. PKM2 regulation by growth factors can redirect glycolytic intermediates into key biosynthetic pathway. Here we show that IGF1 can regulate glycolysis rate, stimulate PKM2 Ser/Thr phosphorylation and decrease cellular pyruvate kinase activity. Upon IGF1 treatment we found an increase of the dimeric form of PKM2 and the enrichment of PKM2 in the nucleus. This effect was associated to a reduction of pyruvate kinase enzymatic activity and was reversed using metformin, which decreases Akt phosphorylation. IGF1 induced an increased nuclear localization of PKM2 and STAT3, which correlated with an increased HIF1α, HK2, and GLUT1 expression and glucose entrapment. Metformin inhibited HK2, GLUT1, HIF-1α expression and glucose consumption. These findings suggest a role of IGFIR/Akt axis in regulating glycolysis by Ser/Thr PKM2 phosphorylation in cancer cells.

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Citations

May 24, 2016·International Journal of Molecular Sciences·Marco TomasettiJiri Neuzil
Oct 14, 2016·Endocrine-related Cancer·Aleksandra M Ochnik, Robert C Baxter
Oct 30, 2016·Cell Cycle·Elisabet CuyàsJavier A Menendez
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Methods Mentioned

BETA
sumoylation
size-exclusion chromatography
nuclear translocation
immunoprecipitation

Software Mentioned

ImageJ

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