DRAKs, novel serine/threonine kinases related to death-associated protein kinase that trigger apoptosis

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.