Sanjo H, Kawai T, Akira S
Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
J Biol Chem. 1998 Oct 30;273(44):29066-71. doi: 10.1074/jbc.273.44.29066.
The present study describes the cloning of two novel serine/threonine kinases termed DRAK1 and DRAK2, whose catalytic domains are related to that of death-associated protein kinase, a serine/threonine kinase involved in apoptosis. Both DRAKs are composed of the N-terminal catalytic domain and the C-terminal domain that is responsible for regulation of kinase activity. DRAK1 and DRAK2 show 59.7% identity and display ubiquitous expression. An in vitro kinase assay revealed that both DRAKs are autophosphorylated and phosphorylate myosin light chain as an exogenous substrate, although the kinase activity of DRAK2 is significantly lower than that of DRAK1. Both DRAKs are exclusively localized to the nucleus. Furthermore, overexpression of both DRAKs induces the morphological changes of apoptosis in NIH 3T3 cells, suggesting the role of DRAKs in apoptotic signaling.
本研究描述了两种名为DRAK1和DRAK2的新型丝氨酸/苏氨酸激酶的克隆，其催化结构域与死亡相关蛋白激酶（一种参与细胞凋亡的丝氨酸/苏氨酸激酶）的催化结构域相关。两种DRAK均由N端催化结构域和负责激酶活性调节的C端结构域组成。DRAK1和DRAK2的一致性为59.7%，且呈现广泛表达。体外激酶分析显示，两种DRAK均能自身磷酸化，并将肌球蛋白轻链作为外源性底物进行磷酸化，尽管DRAK2的激酶活性明显低于DRAK1。两种DRAK都仅定位于细胞核。此外，两种DRAK的过表达均诱导NIH 3T3细胞发生凋亡的形态学变化，提示DRAK在凋亡信号传导中的作用。
