Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse skin epidermal cells.

NEK6 (NIMA-related kinase 6) is a homologue of the Aspergillus nidulans protein NIMA (never in mitosis, gene A). We demonstrate that overexpression of NEK6 induces anchorage-independent transformation of JB6 Cl41 mouse epidermal cells. Tissue arrays and Western immunoblot analysis show that NEK6 is overexpressed in malignant tissues and several cancer cell lines. Our data also show that NEK6 interacts with an oncogenic transcription factor, and phosphorylates on Ser(727), which is important for transcriptional activation. Additional studies using NEK6 mutants suggested that the phosphorylation on both Ser(206) and Thr(210) of NEK6 is critical for duanyu18133 phosphorylation and anchorage-independent transformation of mouse epidermal cells. Notably, knockdown of NEK6 decreased colony formation and duanyu18133 Ser(727) phosphorylation. Based on our findings, the most likely mechanism that can account for this biological effect involves the activation of duanyu18133 through the phosphorylation on Ser(727). Because of the critical role that duanyu18133 plays in mediating oncogenesis, the stimulatory effects of NEK6 on duanyu18133 and cell transformation suggest that this family of serine/threonine kinases might represent a novel chemotherapeutic target.

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