Activation of transglutaminase at calcium levels consistent with a role for this enzyme as a calcium receptor protein.

The sensitivity of tissue transglutaminase to activation by Ca2+ and other cellular factors was investigated using the enzyme purified from rat liver. The inclusion of Mg2+ in the assay system appeared to reduce the Ca2+-requirement of the enzyme when native N,N'-dimethylcasein was used as the protein acceptor substrate. However, when this protein was dephosphorylated, the Ca2+-requirement was unaffected by Mg2+. In addition, using this modified assay, a Km for Ca2+ was calculated to be in the range of 3-4 microM, at least an order of magnitude lower than that obtained with native acceptor substrate. Membrane phospholipids, 1,2-diolein and calmodulin were found not to affect the activation of transglutaminase by Ca2+. The sensitivity of transglutaminase to Ca2+ which we have now demonstrated suggests that this enzyme may directly act as a receptor protein for Ca2+ during stimulus-response coupling mediated by this cation.