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首页> 外文期刊>Molecular and Cellular Biology >Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis
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Cyclin-Dependent Kinase 16/PCTAIRE Kinase 1 Is Activated by Cyclin Y and Is Essential for Spermatogenesis

机译：细胞周期蛋白依赖性激酶16 / PCTAIRE激酶1被细胞周期蛋白Y激活，对于精子发生必不可少

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摘要

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.
机译：细胞周期蛋白依赖性激酶16（CDK16，PCTK1）是一种特征较弱的蛋白激酶，在睾丸和大脑中高表达。在这里，我们报道CDK16被膜相关的细胞周期蛋白Y（CCNY）激活。用蛋白激酶A（PKA）激活蛋白毛喉素治疗转染的人细胞，尽管激酶抑制作用得以促进，但CCNY依赖的CDK16-绿色荧光蛋白（GFP）靶向细胞膜。 CCNY与CDK16的结合需要在激酶结构域的上游区域，并被丝氨酸153的磷酸化（可能的PKA磷酸化位点）抑制。因此，与其他CDK相比，CDK16受磷酸化控制的细胞周期蛋白结合的调控。从鼠睾丸分离出的CDK16未磷酸化，与CCNY相互作用，并表现出激酶活性。为了研究CDK16在体内的功能，我们建立了条件性基因敲除等位基因。缺乏CDK16的小鼠正常发育，但雄性小鼠不育。从附睾中分离出的精子表现出环区变薄和伸长，呈弯曲形状，并且运动力受损。此外，缺乏CDK16的精子头部畸形，胞浆残留过多，提示CDK16在精子中起作用。因此，CDK16是精子发生必不可少的膜靶向CDK。

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