Rapamycin inhibits the phosphorylation of p70 S6 kinase in IL-2 and mitogen-activated human T cells

Biochem Biophys Res Commun. 1992 Aug 14;186(3):1315-21. doi: 10.1016/s0006-291x(05)81549-9.

Abstract

Phosphorylation of 40S ribosomal protein S6 is regulated in part by the mitogen-activated p70 S6 kinase (p70s6k). Following the addition of IL-2 to the IL-2 dependent human cell line Kit225, or mitogenic activation of resting human T cells, a rapid phosphorylation of p70s6k was observed by immunoblotting. Rapamycin (RAP), a potent suppressor of T-cell proliferative responses, markedly inhibited the phosphorylation of p70s6k induced by IL-2 in Kit225 cells or by the mitogens added to resting T cells. Other immunosuppressants such as cyclosporin A or an FK506 analogue were without effect. Moreover, the effect of RAP was restricted to p70s6k; it did not inhibit the phosphorylation of p90rsk, another kinase which utilizes the S6 protein as a substrate. These data indicate for the first time that RAP may target the pathway leading to p70s6k phosphorylation during human T-cell proliferation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies
  • Cell Line
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Ethers, Cyclic / pharmacology
  • Humans
  • Immunoblotting
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 / pharmacology*
  • Ionomycin / pharmacology
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Okadaic Acid
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphorylation
  • Phytohemagglutinins
  • Polyenes / pharmacology*
  • Protein Kinase Inhibitors*
  • Recombinant Proteins / pharmacology
  • Ribosomal Protein S6
  • Ribosomal Protein S6 Kinases
  • Ribosomal Proteins / isolation & purification
  • Ribosomal Proteins / metabolism*
  • Sirolimus
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology
  • Tacrolimus / pharmacology

Substances

  • Antibodies
  • Ethers, Cyclic
  • Immunosuppressive Agents
  • Interleukin-2
  • Peptides
  • Phytohemagglutinins
  • Polyenes
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Ribosomal Protein S6
  • Ribosomal Proteins
  • Okadaic Acid
  • Phorbol 12,13-Dibutyrate
  • Ionomycin
  • Cyclosporine
  • Ribosomal Protein S6 Kinases
  • Phosphoprotein Phosphatases
  • Sirolimus
  • Tacrolimus