The role of phosphatidylinositide-3-kinase in basal mitogen-activated protein kinase activity and cell survival.
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.
Versteeg
H H
HH
Laboratory for Experimental Internal Medicine, Academic Medical Centre, G2-130, Meibergdreef 9, NL-1105 AZ, Amsterdam, The Netherlands.
Evertzen
M W
MW
van Deventer
S J
SJ
Peppelenbosch
M P
MP
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D007527:Isoenzymes / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D008264:Macrophages; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C482127:Map2k1 protein, mouse