Ca2+: a stabilizing component of the transglutaminase activity of Galphah (transglutaminase II).

Gα h (transglutaminase type II; tissue transglutaminase) is a bifunctional enzyme with transglutaminase (TGase) and guanosine triphosphatase (GTPase) activities. The GTPase function of Gα h is involved in hormonal signaling and cell growth while the TGase function plays an important role in apoptosis and in cross-linking extracellular and intracellular proteins. To analyze the regulation of these dual enzymatic activities we examined their calcium-dependence and thermal stability in enzymes from several cardiac sources (mouse heart, and normal, ischemic and dilated cardiomyopathic human hearts). The GTP binding activity of Gα h was markedly inhibited by Ca 2 + whereas the TGase activity was strongly stimulated, suggesting that Ca 2 + acts as a regulator, switching G α h from a GTPase to a TGase. The TGase function of Gα h of both mouse and human hearts was more thermostable in the presence of Ca 2 + .