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.
Takuwa
N
N
Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, Japan.
Zhou
W
W
Kumada
M
M
Takuwa
Y
Y
D042846:CDC2-CDC28 Kinases; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D008934:Mitogens / Q000097:blood; D015513:Oncogene Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D016213:Cyclins; D008934:Mitogens; D015513:Oncogene Proteins; D013729:Terpenes; D019938:Cyclin D1; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D002118:Calcium