Literature search services are currently unavailable. During our hosting provider's UPS upgrade we experienced a hardware failure and are currently working to resolve the issue.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site.

A critical step in S6 kinase 1 (S6K1) activation is Thr(229) phosphorylation in the activation loop by the phosphoinositide-dependent protein kinase (PDK1). Thr(229) phosphorylation requires prior phosphorylation of the Ser/Thr-Pro sites in the autoinhibitory domain and Thr(389) in the linker domain, consistent with PDK1 more effectively catalyzing Thr(229) phosphorylation in a variant harboring acidic residues in these positions (S6K1-E389D(3)E). S6K1-E389D(3)E has high basal activity and exhibits partial resistance to rapamycin and wortmannin, and its activity can be further augmented by mitogens, effects presumably mediated by Thr(229) phosphorylation. However, PDK1-induced Thr(229) phosphorylation is reported to be constitutive rather than phosphatidylinositide 3,4,5-trisphosphate-dependent, suggesting that S6K1-E389D(3)E activity is mediated through a distinct site. Here we use phosphospecific antibodies to show that Thr(229) is fully phosphorylated in S6K1-E389D(3)E in the absence of mitogens and that regulation of S6K1-E389D(3)E activity by mitogens, rapamycin, or wortmannin parallels Ser(371) phosphorylation. Consistent with this observation, a dominant interfering allele of the mammalian target of rapamycin, mTOR, inhibits mitogen-induced Ser(371) phosphorylation and activation of S6K1-E389D(3)E, whereas wild type mTOR stimulates both responses. Moreover, in vitro mTOR directly phosphorylates Ser(371), and this event modulates Thr(389) phosphorylation by mTOR, compatible with earlier in vivo findings.

Pubmed ID: 11914378


  • Saitoh M
  • Pullen N
  • Brennan P
  • Cantrell D
  • Dennis PB
  • Thomas G


The Journal of biological chemistry

Publication Data

May 31, 2002

Associated Grants


Mesh Terms

  • Androstadienes
  • Animals
  • Antibiotics, Antineoplastic
  • Binding Sites
  • Cell Line
  • Enzyme Inhibitors
  • Genes, Dominant
  • Glutathione Transferase
  • Humans
  • Immunoblotting
  • Insulin
  • Phosphorylation
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • Ribosomal Protein S6 Kinases
  • Serine
  • Sirolimus
  • Threonine
  • Transfection