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Translational regulation during activation of porcine peripheral blood lymphocytes: association and phosphorylation of the alpha and gamma subunits of the initiation factor complex eIF-4F.

Abstract
Mature peripheral blood lymphocytes exist in a resting state both in vivo and when maintained in culture, exhibiting low translation rates consistent with their non-proliferative state. Previously we have shown that activation of these quiescent cells with either phorbol ester or concanavalin A leads to a rapid increase in the rate of protein synthesis and phosphate-labelling of initiation factor eIF-4 alpha [Morley, Rau, Kay and Pain (1993) Eur. J. Biochem. 218, 39-48]. We now show that neither the early enhanced translation rate nor the early increased phosphate-labelling of eIF-4 alpha requires the activity of the 70 kDa form of ribosomal protein S6 kinase. In addition, we demonstrate that eIF-4 gamma is phosphorylated in response to cell activation, an event which is correlated with phosphorylation of eIF-4 alpha and enhanced eIF-4F complex formation. In these studies, isoelectric focusing and immunoblot analysis of eIF-4 alpha indicate that phosphate-labelling of eIF-4 alpha following cell activation reflects a modest increase in steady-state phosphorylation, mediated by the enhanced activity of eIF-4 alpha kinase(s) and inhibition of eIF-4 alpha phosphatase activity. In the resting cell, eIF-4 alpha is associated with heat- and acid-stable insulin-responsive protein (PHAS-I; 4E-BP1); following acute stimulation with phorbol ester, there is a 40% decrease in the amount of PHAS-I associated with eIF-4 alpha. Incubation of anti-PHAS-I immunoprecipitates with extracts containing activated or immunprecipitated mitogen-activated protein kinase resulted in a small increase in phosphorylation of recovered PHAS-I and a modest release of eIF-4 alpha from the PHAS-I-eIF-4 alpha complex. These data suggest a possible role for PHAS-I in the regulation of eIF-4F complex formation and the rate of translation in primary cells.
AuthorsS J Morley, V M Pain
JournalThe Biochemical journal (Biochem J) Vol. 312 ( Pt 2) Pg. 627-35 (Dec 01 1995) ISSN: 0264-6021 [Print] England
PMID8526879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • Eukaryotic Initiation Factor-4F
  • Immune Sera
  • Immunosuppressive Agents
  • Macromolecular Substances
  • Peptide Initiation Factors
  • Peptides
  • Phosphates
  • Phosphoproteins
  • Phosphorus Radioisotopes
  • Polyenes
  • Sulfur Radioisotopes
  • Concanavalin A
  • Methionine
  • Protein Kinases
  • eif-4alpha kinase
  • Protein Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Tetradecanoylphorbol Acetate
  • Sirolimus
Topics
  • Amino Acid Sequence
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases (metabolism)
  • Carrier Proteins
  • Concanavalin A (pharmacology)
  • Eukaryotic Initiation Factor-4F
  • Gene Expression Regulation (drug effects)
  • Immune Sera
  • Immunoblotting
  • Immunosuppressive Agents (pharmacology)
  • Kinetics
  • Lymphocyte Activation
  • Lymphocytes (immunology, metabolism)
  • Macromolecular Substances
  • Methionine (metabolism)
  • Molecular Sequence Data
  • Peptide Initiation Factors (biosynthesis, isolation & purification, metabolism)
  • Peptides (chemical synthesis, immunology)
  • Phosphates (metabolism)
  • Phosphoprotein Phosphatases (metabolism)
  • Phosphoproteins (isolation & purification, metabolism)
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Polyenes (pharmacology)
  • Protein Biosynthesis (drug effects)
  • Protein Kinases (metabolism)
  • Protein Serine-Threonine Kinases (isolation & purification, metabolism)
  • Ribosomal Protein S6 Kinases
  • Sirolimus
  • Sulfur Radioisotopes
  • Swine
  • Tetradecanoylphorbol Acetate (pharmacology)

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