Involvement of intact inositol-1,4,5-trisphosphate-sensitive Ca2+ stores in cell cycle progression at the G1/S boundary in serum-stimulated human fibroblasts.

Thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca2+ pump, has been shown to deplete inositol-1,4,5-trisphosphate-sensitive Ca2+ stores. Here we report that when thapsigargin was introduced to serum-stimulated human fibroblasts at a time point just before the G1/S boundary, it completely inhibited expression of cyclin A, activation of p33CDK2 cyclin-dependent kinase and initiation of DNA synthesis. In contrast, the Ca2+ mobilizing ionophore ionomycin was without effect. These findings indicate that Ca2+ inside the inositol-1,4,5-trisphosphate-sensitive Ca2+ stores plays a pivotal role for traverse across the G1/S transition point.