Direct stimulation of NADP + synthesis through Akt-mediated phosphorylation of NAD kinase

Author:

Hoxhaj Gerta1ORCID,Ben-Sahra Issam2,Lockwood Sophie E.1ORCID,Timson Rebecca C.1,Byles Vanessa1,Henning Graham T.1ORCID,Gao Peng3ORCID,Selfors Laura M.4ORCID,Asara John M.5ORCID,Manning Brendan D.1ORCID

Affiliation:

1. Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

2. Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

3. Metabolomics Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.

4. Department of Cell Biology, Harvard Medical School, Boston, MA, USA.

5. Mass Spectrometry Core, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Abstract

Akt produces reducing power The protein kinase Akt provides a link from growth factors to the production of metabolic reducing power within the cell. Hoxhaj et al. discovered that Akt directly phosphorylates nicotinamide adenine dinucleotide kinase (NADK). Catalytic activity of NADK is normally inhibited by its own amino-terminal domain, and phosphorylation by Akt relieved this inhibition. Active NADK produces nicotinamide adenine dinucleotide phosphate (NADP + ). NADP + in turn is required to produce the reduced form of NADP + (NADPH), which is the primary cofactor for reductive metabolism in the cell. Science , this issue p. 1088

Funder

National Institutes of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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