Signal transduction pathways that contribute to increased protein synthesis during T-cell activation

Suzanne Miyamoto, Scot R. Kimball, Brian Safer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Protein synthesis rates were maximally stimulated in human lymphocytes by ionomycin and the phorbol ester PMA (I+P), which promotes proliferation, whereas PMA alone, which does not promote proliferation, stimulated protein synthesis to a lesser degree. Three translation-associated activities, eIF4E phosphorylation, eIF2B activity and 4E-BP1 phosphorylation also increased with stimulation by I+P and PMA, but only 4E-BP1 phosphorylation was differentially stimulated by these conditions. Correspondingly, signaling pathways activated in T cells were probed for their connection to these activities. Immunosuppressants FK506 and rapamycin partially blocked the protein synthesis rate increases by I+P stimulation. FK506 had less of an inhibitory effect with PMA stimulation suggesting that its mechanism mostly affected ionomycin-activated signals. I+P and PMA equally stimulated phosphorylation of ERK1/2, but I+P more strongly stimulated Akt, and p70(S6K) phosphorylation. An inhibitor that blocks ERK1/2 phosphorylation only slightly reduced protein synthesis rates stimulated by I+P or PMA, but greatly reduced eIF4E phosphorylation and eIF2B activity. In contrast, inhibitors of the PI-3 kinase and mTOR pathways strongly blocked early protein synthesis rate stimulated by I+P and PMA and also blocked 4E-BP1 phosphorylation and release of eIF4E suggesting that these pathways regulate protein synthesis activities, which are important for proliferation in T cells. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)28-42
Number of pages15
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1494
Issue number1-2
DOIs
StatePublished - Nov 15 2000
Externally publishedYes

Keywords

  • Activation
  • Immunosuppressants
  • Lymphocytes
  • Signaling
  • Translation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

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