NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms

Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1386-91. doi: 10.1073/pnas.1417290112. Epub 2015 Jan 20.


Nicotinamide adenine dinucleotide phosphate (NADP) is a critical cofactor during metabolism, calcium signaling, and oxidative defense, yet how animals regulate their NADP pools in vivo and how NADP-synthesizing enzymes are regulated have long remained unknown. Here we show that expression of Nadk, an NAD(+) kinase-encoding gene, governs NADP biosynthesis in vivo and is essential for development in Xenopus frog embryos. Unexpectedly, we found that embryonic Nadk expression is dynamic, showing cell type-specific up-regulation during both frog and sea urchin embryogenesis. We analyzed the NAD kinases (NADKs) of a variety of deuterostome animals, finding two conserved internal domains forming a catalytic core but a highly divergent N terminus. One type of N terminus (found in basal species such as the sea urchin) mediates direct catalytic activation of NADK by Ca(2+)/calmodulin (CaM), whereas the other (typical for vertebrates) is phosphorylated by a CaM kinase-dependent mechanism. This work indicates that animal NADKs govern NADP biosynthesis in vivo and are regulated by evolutionarily divergent and conserved CaM-dependent mechanisms.

Keywords: NAD kinase; NADP; calcium signaling; deuterostome animals; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Biological Evolution*
  • Calmodulin / metabolism*
  • DNA Primers
  • HeLa Cells
  • Humans
  • In Situ Hybridization
  • NADP / biosynthesis*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Polymerase Chain Reaction
  • Xenopus / embryology


  • Calmodulin
  • DNA Primers
  • NADP
  • Phosphotransferases (Alcohol Group Acceptor)
  • NAD kinase