NEK10 tyrosine phosphorylates β-catenin to regulate its cytoplasmic turnover.
Nek kinases are involved in regulating several different elements of the centrosomal cycle, primary cilia function, and DNA damage responses. Unlike the other members of the Nek family, which are serine-threonine kinases, Nek10 preferentially targets tyrosines. Nek10 appears to have a broad role in DNA damage responses, regulating a MAPK-activated G2/M checkpoint following UV irradiation and influencing the p53-mediated activation induced by genotoxicity. In an attempt to identify additional Nek10 functions, we characterized the effect of Nek10 deletion in lung cancer cells, where it is relatively highly expressed. Nek10 absence led to an increase in both the signaling and adherens junctions pools of {beta}-catenin. Mechanistically, Nek10 associates with the Axin complex where it phosphorylates {beta}-catenin at Tyr30, located within the regulatory region governing {beta}-catenin turnover. In the absence of Nek10 phosphorylation, GSK3-mediated phosphorylation of {beta}-catenin, a prerequisite for its turnover, was significantly impaired. Stabilization of {beta}-catenin driven by Nek10 loss diminished the ability of cells to form tumorspheres in suspension, grow in soft agar, and colonize mouse lung tissue following tail vein injections.