Activation of Ca2+/calmodulin-dependent protein kinase II is involved in hyperosmotic induction of the human taurine transporter.

We investigated the signaling pathways participating in hyperosmotic regulation of the human taurine transporter (TAUT) by using specific inhibitors of various intracellular signaling molecules. Among them, the specific inhibitor of calcium/calmodulin-dependent protein kinase II (Ca(2+)/CaM kinase II) completely repressed the hyperosmotic regulation of TAUT. The osmosensitive upregulation of TAUT was also significantly inhibited by calmodulin antagonists and calcium-chelators. The increased expression level of TAUT mRNA by hypertonicity was repressed by the specific Ca(2+)/CaM kinase II inhibitor. The activated form of Ca(2+)/CaM kinase II protein could only be detected in Caco-2 cells under hypertonic conditions.