• PMID: 22184064
• Gene Name: CDK16
• Condition: Essential for spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Essential for spermatogenesis

Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis

Mikolcevic P, Sigl R, Rauch V, Hess MW, Pfaller K, Barisic M, Pelliniemi LJ, Boesl M, Geley S.

Cyclin-dependent kinase 16 (CDK16, PCTK1) is a poorly characterized protein kinase, highly expressed in the testis and the brain. Here, we report that CDK16 is activated by membrane-associated cyclin Y (CCNY). Treatment of transfected human cells with the protein kinase A (PKA) activator forskolin blocked, while kinase inhibition promoted, CCNY-dependent targeting of CDK16-green fluorescent protein (GFP) to the cell membrane. CCNY binding to CDK16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential PKA phosphorylation site. Thus, in contrast to other CDKs, CDK16 is regulated by phosphorylation-controlled cyclin binding. CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. To investigate the function of CDK16 in vivo, we established a conditional knockout allele. Mice lacking CDK16 developed normally, but male mice were infertile. Spermatozoa isolated from their epididymis displayed thinning and elongation of the annulus region, adopted a bent shape, and showed impaired motility. Moreover, CDK16-deficient spermatozoa had malformed heads and excess residual cytoplasm, suggesting a role of CDK16 in spermiation. Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. FAU - Mikolcevic, Petra AU - Mikolcevic P AD - Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck, Austria. FAU - Sigl, Reinhard AU - Sigl R FAU - Rauch, Veronika AU - Rauch V FAU - Hess, Michael W AU - Hess MW FAU - Pfaller, Kristian AU - Pfaller K FAU - Barisic, Marin AU - Barisic M FAU - Pelliniemi, Lauri J AU - Pelliniemi LJ FAU - Boesl, Michael AU - Boesl M