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- Title
Calcium-dependent regulation of the cell cycle via a novel MAPK-NF-κ pathway in Swiss 3T3 cells.
- Authors
Sée, Violaine; Rajala, Nina K. M.; Spiller, David G.; White, Michael R. H.
- Abstract
Nuclear factor kappa B (NF-κB) 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-κB-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 sub- sequent NF-κB activation (measured by real-time imaging of the dynamic p65 and IκBα fluorescent fusion proteins), cyclin Dl (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-κB 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-N F-κB pathway in Swiss 3T3 cells.
- Subjects
CALCIUM; SERUM; BLOOD plasma; CELL proliferation; NF-kappa B; CELL growth
- Publication
Journal of Cell Biology, 2004, Vol 166, Issue 5, p661
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200402136