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Signal transduction pathways that contribute to increased protein synthesis during T-cell activation
S Miyamoto1, S R Kimball, B Safer
1Molecular Hematology Branch, NHLBI, Bethesda, MD 20892-1654, USA. smiyamot@ucdavis.edu
Biochimica Et Biophysica Acta
|November 10, 2000
Summary
Stimulating human lymphocytes with ionomycin and PMA maximally increases protein synthesis and T cell proliferation. The PI-3 kinase and mTOR pathways are crucial for regulating these protein synthesis activities.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Protein synthesis is essential for cell proliferation.
- T cell activation involves complex signaling pathways that regulate protein synthesis.
Purpose of the Study:
- To investigate the signaling pathways regulating protein synthesis in human lymphocytes during activation.
- To determine the role of specific signaling molecules in T cell proliferation.
Main Methods:
- Human lymphocytes were stimulated with ionomycin and PMA (I+P) or PMA alone.
- Protein synthesis rates and translation-associated activities (eIF4E, eIF2B, 4E-BP1 phosphorylation) were measured.
- Signaling pathways (ERK1/2, Akt, p70(S6K), PI-3 kinase, mTOR) were probed using specific inhibitors.
Main Results:
- I+P maximally stimulated protein synthesis and proliferation, while PMA alone had a lesser effect.
- 4E-BP1 phosphorylation was differentially stimulated by I+P and PMA.
- Inhibitors of PI-3 kinase and mTOR pathways strongly blocked protein synthesis and 4E-BP1 phosphorylation.
Conclusions:
- The PI-3 kinase and mTOR pathways are critical regulators of protein synthesis supporting T cell proliferation.
- Specific signaling events downstream of ionomycin and PMA stimulation differentially impact translation machinery.