Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Cell Cycle. 2012 Oct 15;11(20):3758-68. doi: 10.4161/cc.21592. Epub 2012 Aug 16.
PCTAIRE kinases (PCTK) are a highly conserved, but poorly characterized, subgroup of cyclin-dependent kinases (CDK). They are characterized by a conserved catalytic domain flanked by N- and C-terminal extensions that are involved in cyclin binding. Vertebrate genomes contain three highly similar PCTAIRE kinases (PCTK1,2,3, a.k.a., CDK16,17,18), which are most abundant in post-mitotic cells in brain and testis. Consistent with this restricted expression pattern, PCTK1 (CDK16) has recently been shown to be essential for spermatogenesis. PCTAIREs are activated by cyclin Y (CCNY), a highly conserved single cyclin fold protein. By binding to N-myristoylated CCNY, CDK16 is targeted to the plasma membrane. Unlike conventional cyclin-CDK interactions, binding of CCNY to CDK16 not only requires the catalytic domain, but also domains within the N-terminal extension. Interestingly, phosphorylation within this domain blocks CCNY binding, providing a novel means of cyclin-CDK regulation. By using these functional characteristics, we analyzed "PCTAIRE" sequence containing protein kinase genes in genomes of various organisms and found that CCNY and CCNY-dependent kinases are restricted to eumetazoa and possibly evolved along with development of a central nervous system. Here, we focus on the structure and regulation of PCTAIREs and discuss their established functions.
PCTAIRE 激酶（PCTK）是一个高度保守但研究较少的细胞周期蛋白依赖性激酶（CDK）亚群。它们的特征是具有保守的催化结构域，两侧为参与细胞周期蛋白结合的 N-和 C-末端延伸。脊椎动物基因组包含三个高度相似的 PCTAIRE 激酶（PCTK1、2、3，也称为 CDK16、17、18），它们在大脑和睾丸的有丝分裂后细胞中最为丰富。与这种受限的表达模式一致，最近发现 PCTK1（CDK16）对于精子发生是必不可少的。PCTAIRE 被高度保守的单细胞周期蛋白折叠蛋白 cyclin Y（CCNY）激活。通过与 N-豆蔻酰化的 CCNY 结合，CDK16 被靶向到质膜。与传统的细胞周期蛋白-CDK 相互作用不同，CCNY 与 CDK16 的结合不仅需要催化结构域，还需要 N-末端延伸中的结构域。有趣的是，该结构域内的磷酸化会阻止 CCNY 的结合，提供了一种新的细胞周期蛋白-CDK 调节方式。利用这些功能特征，我们分析了各种生物体基因组中含有“PCTAIRE”序列的蛋白激酶基因，发现 CCNY 和 CCNY 依赖性激酶仅限于真后生动物，并且可能随着中枢神经系统的发育而进化。在这里，我们重点关注 PCTAIRE 的结构和调节，并讨论其已确立的功能。
