Requirement of the serine-threonine kinase Akt for heat treatment-induced activation of p70 S6 kinase.
p70 S6 kinase plays an important role in growth factor-induced translational control and in cell cycle progression. Although the mechanism of p70 S6 kinase regulation is not fully understood, phosphorylation of serine and threonine residues of the enzyme is essential for its activation. The possible role of the serine-threonine kinase Akt in the activation of p70 S6 kinase induced by exposure of cells to heat has now been investigated. Overexpression of a mutant Akt1 (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine was shown to exert a dominant negative effect on Akt activation induced by platelet-derived growth factor (PDGF) or by heat treatment in CHO cells. Akt-AA also inhibited p70 S6 kinase activation induced by these stimuli. However, Akt-AA had no effect on the activation of p70 S6 kinase induced by 12-O-tetradecanoylphorbol 13-acetate, which did not stimulate Akt activity in these cells. These data suggest that Akt is required for heat treatment-induced activation of p70 S6 kinase.
Kuroda
S
S
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Ogawa
W
W
Kitamura
T
T
Konishi
H
H
Kikkawa
U
U
Kasuga
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D005822:Genetic Vectors; D006358:Hot Temperature; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D013755:Tetradecanoylphorbol Acetate