A Ca2+-Calmodulin-Dependent Protein Kinase II Inhibitor Suppresses Cell Migration of CD38-Expressing Human Embryonic Kidney Cells: A Preliminary Report

Abstract

CD38 produces Ca²⁺-mobilizing second messengers, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate, at its catalytic site. The molecular mechanism of enzymatic activation modulation has not been completely elucidated. We hypothesized that the β isoform of Ca²⁺-calmodulin-dependent protein kinase II (CaMKII) has a modulator activity on CD38. Functional interaction between CD38 and CAMKIIβ was studied, focusing on cell migration and Ca²⁺ signaling in wound-healing assay. The healing border showed irregular characteristics, with protrusions in HA-CD38 cDNA-transfected samples, and CD38-expressed cells were localized at the tip, likely to behave as 'leader cells,' and at the bottom and edge of protrusions. However, HA-CD38 cDNA-transfected samples treated with a CaMKII inhibitor, KN-62, showed a rather smooth front with less migration during the healing process, and CD38-expressed cells were diffusely localized. Such healing phenomena were not apparent in mock-transfected HEK cells. These results indicate that CD38-dependent cell migratory characteristics are modulated by CaMKII.