The Apoptosis-Inducing Protein Kinase DRAK2 Is Inhibited in a Calcium-Dependent Manner by the Calcium-Binding Protein CHP

Calcineurin homologous protein (CHP) is an EF-hand Ca2+-binding protein capable of interacting with various cellular proteins including Na+/H+ exchangers, kinesin-related proteins, and apoptosis-inducing protein kinase DRAK2. We investigated the role of CHP on the DRAK2 protein kinase in vitro. CHP significantly reduced (~85% inhibition) the kinase activity of DRAK2 for both autophosphorylation and phosphorylation of exogenous substrate (myosin light chain). The inhibitory effect of CHP was dependent on the presence of Ca2+, whereas the interaction between CHP and DRAK2 was not Ca2+-dependent. These observations suggest that CHP negatively regulates the apoptosis-inducing protein kinase DRAK2 in a manner that depends on intracellular Ca2+-concentration.