p70 S6 kinase is activated by sodium arsenite in adult rat cardiomyocytes: roles for phosphatidylinositol 3-kinase and p38 MAP kinase.
p70 S6 kinase (p70 S6k) is important in regulating a variety of cellular functions including mRNA translation and cell cycle progression and is activated by mitogens and hormones. Unexpectedly, we have found that, in adult rat cardiomyocytes, arsenite, which generally induces stress responses, markedly and rapidly activates p70 S6k. This activation of p70 S6k is completely blocked by rapamycin but only partially prevented by inhibitors of phosphatidylinositol 3-kinase. In trying to delineate the mechanism underlying this effect, we found that arsenite did not activate protein kinase B, JNK or MAP kinase, but did activate p38 MAP kinase in cardiac myocytes. A specific inhibitor of p38 MAP kinase (SB203580) partially attenuated the stimulation of p70 S6k by arsenite. These data indicate that the activation of p70 S6k by arsenite involves p38 MAP kinase and phosphatidylinositol 3-kinase but not PKB.
Wang
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Research School of Biosciences, University of Kent at Canterbury, United Kingdom.
Proud
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D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002469:Cell Separation; D004789:Enzyme Activation / Q000187:drug effects; D039561:Eukaryotic Initiation Factor-4E; D008297:Male; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010448:Peptide Initiation Factors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D011090:Polyenes / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D012269:Ribosomal Proteins / Q000378:metabolism*; D020123:Sirolimus; D017670:Sodium Compounds / Q000494:pharmacology*; D013312:Stress, Physiological / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D039561:Eukaryotic Initiation Factor-4E; D020928:Mitogen-Activated Protein Kinases; D010448:Peptide Initiation Factors; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D012269:Ribosomal Proteins; D020123:Sirolimus; D017670:Sodium Compounds; D048051:p38 Mitogen-Activated Protein Kinases; C017947:sodium arsenite