Abstract
Hippocalcin is a member of the neuronal calcium sensors (NCS) family predominantly expressed in the hippocampal pyramidal cells. We have found that hippocalcin binds to C-terminal region of mixed leneage kinase (MLK) 3, and inhibits its phosphorylation state. Here we analyzed activity of MLK3 in hippocalcin deficient mice because phosphorylation events in MLK3 play crucial roles in its activation process. Immunoblot analysis using substrate specific anti-phospho-antibody revealed that MKK3, one of the substrate of MLK3, in hippocalcin deficient mice was higher phosphorylated than that in wild type. Kinase activity of immunoprecipitated MLK3 was examined using bacterially expressed MKK4 as a substrate. The resting MLK3 activity in hippocalcin deficient mice was higher than that in wild type. These observations suggest that the binding of hippocalcin to C-terminal domain of MLK3 keeps MLK3 in inactive state via regulating MLK3 phosphorylation state. [Jpn J Physiol 55 Suppl:S80 (2005)]
