Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis Petra Mikolcevic a , Reinhard Sigl a , Veronika Rauch a , Michael W. Hess b , Kristian Pfaller b , Marin Barisic a , * , Lauri J. Pelliniemi c , Michael Boesl d and Stephan Geley a a Division of Molecular Pathophysiology, Biocenter b Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria c Laboratory of Electron Microscopy, University of Turku, Turku, Finland d Max Planck Institute of Biochemistry, Martinsried, Germany ABSTRACT 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.
Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis
Abstract
Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis Petra Mikolcevic a , Reinhard Sigl a , Veronika Rauch a , Michael W. Hess b , Kristian Pfaller b , Marin Barisic a , * , Lauri J. Pelliniemi c , Michael Boesl d and Stephan Geley a a Division of Molecular Pathophysiology, Biocenter b Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria c Laboratory of Electron Microscopy, University of Turku, Turku, Finland d Max Planck Institute of Biochemistry, Martinsried, Germany ABSTRACT 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.Preview Only. This article cannot be rented because we do not currently have permission from the publisher.
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Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis
Mikolcevic, Petra; Sigl, Reinhard; Rauch, Veronika; Hess, Michael W.; Pfaller, Kristian; Barisic, Marin; Pelliniemi, Lauri J.; Boesl, Michael; Geley, Stephan
Follow Molecular and Cellular Biology
, Volume 32 (4): 868
American Society For Microbiology – Feb 15, 2012
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