NEK6, Active

Nek6 is a serine/threonine kinase that is a member of the Nek family of protein kinases that share an amino-terminal catalytic domain related to NIMA (never in mitosis, gene A) family (1). Nek6 is a nuclear and cytoplasmic kinase that is required for mitotic progression of human cells. Nek6 is phosphorylated and activated during M phase of the cell cycle (2). Inhibition of Nek6 function by either overexpression of an inactive Nek6 mutant or elimination of endogenous Nek6 by siRNA arrests cells in M phase and triggers apoptosis suggesting that Nek6 is required for metaphase-anaphase transition. Nercc1/Nek9 binds to Nek6 and is likely to be responsible for the activation of Nek6 during mitosis representing a new signaling pathway that regulates mitotic progression (3). Northern blot analysis shows that Nek6 transcript is ubiquitously expressed with the highest expression found in the heart and skeletal muscle. Nek6 effectively phosphorylates histones H1 and H3, but not casein suggesting that, unlike other mammalian NIMA-related kinases, Nek6 is a mitotic histone kinase which regulates chromatin condensation in mammalian cells. In addition, Nek6 phosphorylates p70 S6 kinase at Thr412 and other sites and activates the p70 S6 kinase in vitro and in vivo, in a manner synergistic with PDK1 (4). Kinase-inactive Nek6 interferes with insulin activation of p70 S6 kinase implicating Nek6 as a possible physiologic regulator of the p70 S6 kinase.