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 Ca(2+)-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 (approximately 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 Ca(2+), whereas the interaction between CHP and DRAK2 was not Ca(2+)-dependent. These observations suggest that CHP negatively regulates the apoptosis-inducing protein kinase DRAK2 in a manner that depends on intracellular Ca(2+)-concentration.
Kuwahara
Hiroshi
H
Department of Biological Science, Graduate School of Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043.
Kamei
Jun-ichi
J
Nakamura
Norihiro
N
Matsumoto
Miho
M
Inoue
Hiroki
H
Kanazawa
Hiroshi
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D019556:COS Cells; D019703:Calcineurin / Q000235:genetics; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; C115489:STK17B protein, human; D019703:Calcineurin; D002118:Calcium