CELL CYCLE-DEPENDENT EXPRESSION OF NEK2, A NOVEL HUMAN PROTEIN-KINASERELATED TO THE NIMA MITOTIC REGULATOR OF ASPERGILLUS-NIDULANS

The serine/threonine protein kinase NIMA of Aspergillus nidulans is re quired for entry into mitosis and may function in parallel to the univ ersal mitotic inducer p34cdc2. Here, we report the isolation of comple mentary DNAs encoding Nek2 and Nek3, two novel human protein kinases s tructurally related to NIMA. Sequence comparisons revealed several uni que features which may define a family of NIMA-related protein kinases . Nek2 was chosen for further study since it represents the closest kn own mammalian relative of NIMA. Chromosomal mapping of the nek2 gene i dentified two independent loci on chromosomes 1 and 14, and Northern b lot analyses revealed the expression of two distinct mRNAs of approxim ately 2.4 and 4.7 kilobases in all human cell lines examined. In HeLa cells synchronized by both drug arrest and elutriation, a strikingly c ell cycle-dependent pattern of Nek2 expression could be observed; Nek2 protein was almost undetectable during G1 but accumulated progressive ly throughout S, reaching maximal levels in late G2. These observation s demonstrate that Nek2 resembles Aspergillus NIMA, not only in its ca talytic domain, but also in its cell cycle-dependent expression. Hence , the human Nek2 protein kinase may also function at the onset of mito sis.