Nek6

Nek6 is a cell-cycle-regulated serine/threonine protein kinase of the NIMA family that accumulates and is activated during mitosis. Nek6 consists almost entirely of a catalytic domain, and (together with the highly similar Nek7) it is the only NIMA-family member that lacks an extended regulatory domain. Both Nek6 and Nek7 bind to and are phosphorylated by the related Nek9 protein kinase. This phosphorylation results in direct activation of Nek6 and Nek7. Binding of Nek6 to Nek9 occurs in vivo exclusively in mitosis, when Nek9 is activated, thus suggesting that the two kinases form a mitotic signaling module. Mitotic Nek6 activation is prevented by the DNA-damage response, possibly through direct phosphorylation of Nek6 by the Chk1 and Chk2 kinases. Nek6 is necessary for correct progression through mitosis; interfering with the kinase leads to metaphase delays, abnormal mitotic spindle structure and chromosome segregation, and cytokinetic defects. This may be at least partially explained by the fact that the mitotic kinesin Eg5 is a substrate for Nek6, and that Eg5 phosphorylation at the Nek6-modified site is necessary for mitotic spindle formation.