KN‐62: A Specific Ca²⁺/calmodulin‐dependent Protein Kinase Inhibitor as a Putative Function‐searching Probe for Intracellular Signal Transduction

The relationship between changes in intracellular free calcium concentration (Ca i 2+ ) and cell functions is becoming more clear, since it has become possible to measure Ca i 2+ in a living cell. There are, however, still unsolved questions concerning the role of Ca 2+ in cellular signal transmission. It is not easy to relate Ca 2+ signalling to the functions of a living cell. It is possible to control the amount of Ca 2+ using calcium channel blockers, but it is still almost impossible to elucidate the relationship between Ca 2+ and cellular functions by controlling Ca 2+ signalling. One approach to solving this problem is to develop and use protein kinase inhibitors. Inhibitors specific to Ca 2+ /calmodulin‐dependent protein phosphorylation, which is one of the important network systems of the Ca 2+ signalling, attract interest among many researchers. The substances that can control Ca 2+ signalling include: 1) calcium channel blockers, 2) calmodulin antagonists, and 3) Ca 2+ /calmodulin‐dependent protein kinase inhibitors. Each substance has a different site of action. In this article, the action of KN‐62, an inhibitor specific for Ca 2+ /calmodulin protein kinases (CaM kinases) will be described.