Rapamycin-sensitive phosphorylation of ribosomal protein S17 by p70 S6 kinase.
The immunosuppressant rapamycin selectively inhibits the phosphorylation of the ribosomal protein S6. We demonstrate that rapamycin also inhibits the phosphorylation of another ribosomal protein identified by isolation and microsequencing as ribosomal protein S17. The phosphorylation of S17 in T- and B-cell lines is specifically inhibited by rapamycin. IL-3 induces the phosphorylation of S17 in the IL3-responsive cell line, BaF3, and this phosphorylation is inhibited by rapamycin. Purified preparations of recombinant S17 are phosphorylated in vitro by immunoprecipitated p70 S6 kinase. Finally, recombinant S17 is phosphorylated by cellular fractions containing p70 S6 kinase, whereas no other cellular fractions were found to contain any significant S17 kinase activity. These data suggest that the ribosomal protein S17 is a substrate for p70 S6 kinase both in vitro and in vivo and that S17 may be involved in mediating the inhibitory effects of rapamycin on protein translation in cells of different lineages.
Patel
H R
HR
Department of Pediatrics, National Jewish Center for Immunology, Denver, Colorado 80206, USA.
Terada
N
N
Gelfand
E W
EW
D001402:B-Lymphocytes; D002460:Cell Line; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned; D005982:Glutathione Transferase; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011090:Polyenes / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D012269:Ribosomal Proteins / Q000378:metabolism*; D020123:Sirolimus; D013601:T-Lymphocytes
D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010710:Phosphates; D011090:Polyenes; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; C037084:ribosomal protein S17; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus