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 language | English (US) |
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Pages (from-to) | 28-42 |
Number of pages | 15 |
Journal | Biochimica et Biophysica Acta - Gene Structure and Expression |
Volume | 1494 |
Issue number | 1-2 |
DOIs | |
State | Published - Nov 15 2000 |
Externally published | Yes |
Keywords
- Activation
- Immunosuppressants
- Lymphocytes
- Signaling
- Translation
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Structural Biology
- Biophysics