Calcium-dependent regulation of the cell cycle via a novel MAPK--NF-kappaB pathway in Swiss 3T3 cells.
Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation and transformation. We investigated the role of the serum-induced intracellular calcium increase in the NF-kappaB--dependent cell cycle progression in Swiss 3T3 fibroblasts. Noninvasive photoactivation of a calcium chelator (Diazo-2) was used to specifically disrupt the transient rise in calcium induced by serum stimulation of starved Swiss 3T3 cells. The serum-induced intracellular calcium peak was essential for subsequent NF-kappaB activation (measured by real-time imaging of the dynamic p65 and IkappaBalpha fluorescent fusion proteins), cyclin D1 (CD1) promoter-directed transcription (measured by real-time luminescence imaging of CD1 promoter-directed firefly luciferase activity), and progression to cell division. We further showed that the serum-induced mitogen-activated protein kinase (MAPK) phosphorylation is calcium dependent. Inhibition of the MAPK- but not the PtdIns3K-dependent pathway inhibited NF-kappaB signaling, and further, CD1 transcription and cell cycle progression. These data suggest that a serum-dependent calcium signal regulates the cell cycle via a MAPK--NF-kappaB pathway in Swiss 3T3 cells.
Centre for Cell Imaging, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, England, UK.
Violaine
V
Sée
Nina K M
NK
Rajala
David G
DG
Spiller
Michael R H
MR
White
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002614:Chelating Agents / Q000494:pharmacology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003979:Diazonium Compounds; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010642:Phenoxyacetates; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D041701:Swiss 3T3 Cells; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D001798:Blood Proteins; D002352:Carrier Proteins; D002614:Chelating Agents; D003979:Diazonium Compounds; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C000606205:Nfkbia protein, mouse; D010642:Phenoxyacetates; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C063685:diazo-2; D019938:Cyclin D1; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D002118:Calcium