Galactose-1 phosphate uridylyltransferase (GalT) gene: A novel positive regulator of the PI3K/Akt signaling pathway in mouse fibroblasts

Biochemical and Biophysical Research Communications
Bijina BalakrishnanK Lai

Abstract

The vital importance of the Leloir pathway of galactose metabolism has been repeatedly demonstrated by various uni-/multicellular model organisms, as well human patients who have inherited deficiencies of the key GAL enzymes. Yet, other than the obvious links to the glycolytic pathway and glycan biosynthetic pathways, little is known about how this metabolic pathway interacts with the rest of the metabolic and signaling networks. In this study, we compared the growth and the expression levels of the key components of the PI3K/Akt growth signaling pathway in primary fibroblasts derived from normal and galactose-1 phosphate uridylyltransferase (GalT)-deficient mice, the latter exhibited a subfertility phenotype in adult females and growth restriction in both sexes. The growth potential and the protein levels of the pAkt(Thr308), pAkt(Ser473), pan-Akt, pPdk1, and Hsp90 proteins were significantly reduced by 62.5%, 60.3%, 66%, 66%, and 50%, respectively in the GalT-deficient cells. Reduced expression of phosphorylated Akt proteins in the mutant cells led to diminished phosphorylation of Gsk-3β (-74%). Protein expression of BiP and pPten were 276% and 176% higher respectively in cells with GalT-deficiency. Of the 24 genes interrogat...Continue Reading

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Citations

Sep 16, 2017·Journal of Inherited Metabolic Disease·Jo M VanoevelenM Estela Rubio-Gozalbo
Jan 20, 2018·Journal of Inherited Metabolic Disease·Tatiana YuzyukNicola Longo
Dec 7, 2019·Journal of Inherited Metabolic Disease·Minela HaskovicM Estela Rubio-Gozalbo
Sep 21, 2018·Orphanet Journal of Rare Diseases·Hugh-Owen ColhounEileen P Treacy
Feb 3, 2021·Journal of Personalized Medicine·Britt DelnoyMaria Estela Rubio-Gozalbo

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