Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Proteins / pharmacology
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Calcium / metabolism*
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Calcium Signaling / drug effects
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Calcium Signaling / genetics*
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Carrier Proteins / metabolism
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Cell Cycle / drug effects
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Cell Cycle / genetics*
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Cell Division / drug effects
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Cell Division / genetics
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Chelating Agents / pharmacology
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Diazonium Compounds
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / genetics*
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Mice
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Neoplasm Proteins / metabolism
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Phenoxyacetates
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation / drug effects
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / genetics
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Swiss 3T3 Cells
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Transcription Factor RelA
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
Substances
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Blood Proteins
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Carrier Proteins
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Chelating Agents
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Diazonium Compounds
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I-kappa B Proteins
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NF-kappa B
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Neoplasm Proteins
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Nfkbia protein, mouse
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Phenoxyacetates
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Rela protein, mouse
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Transcription Factor RelA
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diazo-2
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Cyclin D1
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NF-KappaB Inhibitor alpha
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Phosphatidylinositol 3-Kinases
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Mitogen-Activated Protein Kinase 1
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Calcium