Abstract
Phosphatidylinositide-3-OH-kinase (PI 3-kinase) is an upstream activator of p42/p44 mitogen-activated protein kinase (MAPK), but the role of PI 3-kinase-dependent MAPK remains obscure. Here we demonstrate that in a variety of different cell types, PI 3-kinase inhibition results in an inhibition of MAPK in unstimulated cells but does not interfere with growth factor-, or TPA-induced MAPK activity. Furthermore, inhibition of either PI 3-kinase or MEK/MAPK results in cell death in serum-starved cells. We concluded that basal, but not induced MAPK activity is mediated by PI 3-kinase and that this PI 3-kinase-mediated MEK/MAPK activity is essential for cell survival in quiescent cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / pharmacology
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Animals
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CHO Cells
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COS Cells
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Cell Line
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Cell Survival
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Chromones / pharmacology
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Cricetinae
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Enzyme Inhibitors / pharmacology
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Fibroblasts
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Isoenzymes / metabolism
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MAP Kinase Kinase 1
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Macrophages
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Mice
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / metabolism*
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Protein Serine-Threonine Kinases*
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Wortmannin
Substances
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Androstadienes
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Chromones
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Enzyme Inhibitors
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Isoenzymes
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase 1
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Map2k1 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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Wortmannin