Direct stimulation of NADP <sup>+</sup> synthesis through Akt-mediated phosphorylation of NAD kinase

Gerta Hoxhaj(Harvard University), Issam Ben‐Sahra(Northwestern University), Sophie E. Lockwood(Harvard University), Rebecca C. Timson(Harvard University), Vanessa Byles(Harvard University), Graham T. Henning(Harvard University), Peng Gao(Robert H. Lurie Comprehensive Cancer Center of Northwestern University), Laura M. Selfors(Harvard University), John M. Asara(Beth Israel Deaconess Medical Center), Brendan D. Manning(Harvard University)
Science
March 7, 2019
Cited by 142Open Access
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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


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