Publication Date:
2019
Description:
〈p〉Nicotinamide adenine dinucleotide phosphate (NADP〈sup〉+〈/sup〉) is essential for producing NADPH, the primary cofactor for reductive metabolism. We find that growth factor signaling through the phosphoinositide 3-kinase (PI3K)–Akt pathway induces acute synthesis of NADP〈sup〉+〈/sup〉 and NADPH. Akt phosphorylates NAD kinase (NADK), the sole cytosolic enzyme that catalyzes the synthesis of NADP〈sup〉+〈/sup〉 from NAD〈sup〉+〈/sup〉 (the oxidized form of NADH), on three serine residues (Ser〈sup〉44〈/sup〉, Ser〈sup〉46〈/sup〉, and Ser〈sup〉48〈/sup〉) within an amino-terminal domain. This phosphorylation stimulates NADK activity both in cells and directly in vitro, thereby increasing NADP〈sup〉+〈/sup〉 production. A rare isoform of NADK (isoform 3) lacking this regulatory region exhibits constitutively increased activity. These data indicate that Akt-mediated phosphorylation of NADK stimulates its activity to increase NADP〈sup〉+〈/sup〉 production through relief of an autoinhibitory function inherent to its amino terminus.〈/p〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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