A CENTROSOMAL FUNCTION FOR THE HUMAN NEK2 PROTEIN-KINASE, A MEMBER OFTHE NIMA FAMILY OF CELL-CYCLE REGULATORS

Nek2, a mammalian protein kinase of unknown function, is closely relat ed to the mitotic regulator NIMA of Aspergillus nidulans, Here we show by both immuno-fluorescence microscopy and biochemical fractionation that human Nek2 localizes to the centrosome, Centrosome association oc curs throughout the cell cycle, including all stages of mitosis, and i s independent of microtubules, Overexpression of active Nek2 induces a striking splitting of centrosomes, whereas prolonged expression of ei ther active or inactive Nek2 leads to dispersal of centrosomal materia l and loss of a focused microtubule-nucleating activity. Surprisingly, this does not prevent entry into mitosis, as judged by the accumulati on of mitotically arrested cells induced by coexpression of a non-dest ructible B-type cyclin. These results bear on the dynamic function of centrosomes at the onset of mitosis, Moreover, they indicate that one function of mammalian Nek2 relates to the centrosome cycle and thus pr ovide a new perspective on the role of NIMA-related kinases.