ZAK包括一個 kinase domain，leucine zipper (LZ)以及一個sterile-alpha motif (SAM) domain，是屬於MAP kinase kinase kinase (MAP3K)。ZAK 以證實是經由下游基因MKK7來間接活化JNK/SAPK這條路徑，進而影響到細胞生長停滯 (arrest)。ZAK藉由yeast-two hybrid system找到了與ZAK相關的蛋白質，其中並且找到了與small GTPase相關的RhoGDIβ。Rho GDP-dissociation inhibitors (RhoGDIs)為一內生性(endogenous)的Rho GTPase的抑制物 (inhibitor)，在調節RhoGTPase在生物活性 (biological activity)上扮演重要的角色。已知有三種形式的RhoGDIs，RhoGDIα(RhoGDI, RhoGDI-1)，RhoGDIβ(D4/Ly-GDI, RhoGDI-2)以及RhoGDIγ (RhoGDI-3)。將RhoGDIβ利用GST-pull down assay證明了ZAK與RhoGDIβ之間的關係。並且藉由Tet-on system來測試後發現，RhoGDIβ對於一些細胞週期調節蛋白 (cell cycle regulator protein)有所影響。除此之外，也證實了RhoGDIβ對於small GTPase的Rac有影響。然而ZAK與RhoGDIβ之間對於Rac的調控機制也是有所影響的。另外，我們也發現了RhoGDIβ對於H9C2 cell有產生細胞型態的影響，也對於細胞的生長有所影響。在一些研究報告中已知RhoGDIs可以調控Rho proteins在細胞內存在位置 (subcellular localization)。在我們的實驗中也發現，RhoGDIβ確實會影響Rac在細胞膜或細胞質內的移動。因此我們知道了ZAK與RhoGDIβ在細胞中的功能與影響。未來我們也希望瞭解ZAK與RhoGDIβ是如何調控Rac，而在ZAK的存在之下又是如何影響Rac的表現。對於ZAK調控RhoGDIβ的機制有何重要性。
The leucine-zipper (LZ) and sterile- motif (SAM) kinase (ZAK) belongs to the MAP kinase kinase kinase (MAP3K) when upon over expression in mammalian cells activates the JNK/SAPK pathway, comprising a group of highly related serine / threonine kinase. That ZAK activates JNK / SAPK mediated by downstream taget, MKK7. The report present suggests a schematic pathway of ZAK→MKK7→JNK→cell arrest. By substrative yeast two hybrid system to cloned a RhoGDI- homologous cDNA, named RhoGDIβ. Rho GDP-dissociation inhibitors (RhoGDIs), endogenous inhibitors of Rho GTPase, play an important role in regulating the biological activitys of Rho protein. As yet, only three RhoGDIs have been described：RhoGDIα(RhoGDI, RhoGDI-1), RhoGDIβ(D4 / Ly-GDI, RhoGDI- 1), and RhoGDIγ(RhoGDI-3). We used GST-pull down to prove that the relationship between ZAK and RhoGDIβ. And by tet-on system suggest that RhoGDIβhave effect on some Cell cycle regulator protein. Besides, it also identifies RhoGDIβ regulat the small GTPase protein, Rac.
