S6K1 is acetylated at lysine 516 in response to growth factor stimulation.
The 70kDa ribosomal protein S6 kinase 1 (S6K1) plays important roles in the regulation of protein synthesis, cell growth and metabolism. S6K1 is activated by the phosphorylation of multiple serine and threonine residues in response to stimulation by a variety of growth factors and cytokines. In addition to phosphorylation, we have recently shown that S6K1 is also targeted by lysine acetylation. Here, using tandem mass spectrometry we have mapped acetylation of S6K1 to lysine 516, a site close to the C-terminus of the kinase that is highly conserved amongst vertebrate S6K1 orthologues. Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation. Although S6K1 acetylation and phosphorylation are both induced by growth factor stimulation, these events appear to be functionally independent. Indeed, experiments using inhibitors of S6K1 activation and exposure of cells to various stresses indicate that S6K1 acetylation can occur in the absence of phosphorylation and vice versa. We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling.
Fenton
Tim R
TR
Department of Structural and Molecular Biology, University College London, Gower Street, Darwin Building, London WC1E 6BT, UK.
Gwalter
Jodie
J
Cramer
Rainer
R
Gout
Ivan T
IT
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D007334:Insulin-Like Growth Factor I; D008239:Lysine; D010982:Platelet-Derived Growth Factor; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C075278:platelet-derived growth factor A; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1