| Death-associated protein kinase (DAPK1) is a Ca2+/calmodulin-regulated serine/threonine kinase that participates in a wide range of apoptotic signals including interferon-γ, tumor necrosis factor α, Fas, activated c-Myc, and detachment from the extracellular matrix. In addition to the kinase domain and calmodulin regulatory segment, DAPK1 also has eight ankyrin repeats, a cytoskeleton binding region, and a conserved death domain (1-3). Deletion of the calmodulin-regulatory domain generates a constitutively active mutant kinase. Ectopic expression of wild-type DAPK1 induced cell death in HeLa cells. Conversely, expression of a catalytically inactive mutant protected cells from interferon-γ-induced cell death (4). The catalytic domain of DAPK1 has very high sequence similarity to vertebrate myosin light chain kinase (MLCK) and a RXX(S/T)X motif derived from myosin light chain protein was shown to be phosphorylated in vitro by DAPK1 (5). |
