Interplay between MEK and PI3 kinase signaling regulates the subcellular localization of protein kinases ERK1/2 and Akt upon oxidative stress.
ERK and Akt kinases are key components that participate in numerous regulatory processes, including the response to stress. Using novel tools for quantitative immunofluorescence, we show that oxidant exposure controls the intracellular activation and localization of ERK1/2 and Akt. Oxidative stress alters the nuclear/cytoplasmic levels of the kinases, drastically changing phospho-ERK1/2 and phospho-Akt(Ser473) levels in the nucleus. Moreover, pharmacological inhibition of PI3 kinase modulates the intracellular distribution of phospho-ERK1/2, whereas MEK inhibition affects phospho-Akt(Thr308) and phospho-Akt(Ser473). Our studies identify a new signaling link in the nucleus of stressed cells, where changes in phospho-ERK1/2 levels correlate directly with changes in phospho-Akt(Ser473).
Kodiha
Mohamed
M
Department of Physiology, McGill University, Montreal, PQ, Canada.
Bański
Piotr
P
Stochaj
Ursula
U
D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; C499517:FOXO3 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one