High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230026, China.
Int J Mol Sci. 2019 Sep 30;20(19):4852. doi: 10.3390/ijms20194852.
STK16, reported as a Golgi localized serine/threonine kinase, has been shown to participate in multiple cellular processes, including the TGF-β signaling pathway, TGN protein secretion and sorting, as well as cell cycle and Golgi assembly regulation. However, the mechanisms of the regulation of its kinase activity remain underexplored. It was known that STK16 is autophosphorylated at Thr185, Ser197, and Tyr198 of the activation segment in its kinase domain. We found that STK16 localizes to the cell membrane and the Golgi throughout the cell cycle, but mutations in the auto-phosphorylation sites not only alter its subcellular localization but also affect its kinase activity. In particular, the Tyr198 mutation alone significantly reduced the kinase activity of STK16, abolished its Golgi and membrane localization, and affected the cell cycle progression. This study demonstrates that a single site autophosphorylation of STK16 could affect its localization and function, which provides insights into the molecular regulatory mechanism of STK16's kinase activity.
STK16 被报道为一种定位于高尔基体的丝氨酸/苏氨酸激酶，它参与了多种细胞过程，包括 TGF-β 信号通路、TGN 蛋白分泌和分拣，以及细胞周期和高尔基体组装的调节。然而，其激酶活性的调节机制仍未得到充分探索。已知 STK16 在其激酶结构域的激活片段中 Thr185、Ser197 和 Tyr198 处发生自身磷酸化。我们发现 STK16 在整个细胞周期中定位于细胞膜和高尔基体，但自动磷酸化位点的突变不仅改变了它的亚细胞定位，而且还影响了它的激酶活性。特别是，单独的 Tyr198 突变显著降低了 STK16 的激酶活性，使其高尔基体和膜定位失活，并影响细胞周期进程。本研究表明，STK16 的单个位点自身磷酸化可以影响其定位和功能，这为 STK16 的激酶活性的分子调节机制提供了新的见解。
