Increased rate of phosphorylation-dephosphorylation of the translational initiation factor eIF-4E correlates with the induction of protein and glycoprotein biosynthesis in activated B lymphocytes

W. Rychlik, J. S. Rush, R. E. Rhoads, C. J. Waechter

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44 Scopus citations

Abstract

A 10-50-fold, biphasic increase in the rate of 32P(i) labeling of eIF-4E was closely correlated with the induction of protein and glycoprotein biosynthesis when resting murine splenic B lymphocytes (B cells) were activated by bacterial lipopolysaccharide or the combination of phorbol 12-myristate 13-acetate and ionomycin. The fraction of eIF-4E which was phosphorylated only increased from 46% in resting cells to 83% in lipopolysaccharide-activated cells. This discrepancy between the increase in the fraction of phosphorylated eIF-4E and the increase in 32P(i) labeling suggested that the phosphoryl group of eIF-4E turns over slowly in resting B cells compared with activated cells. The turn-over rate for the eIF-4E phosphate moiety in lipopolysaccharide-activated cells was rapid (t( 1/2 ) = 2 h) in comparison to the eIF-4E polypeptide chain, which did not turn over detectably in 6 h. Neither protein kinase C nor a cyclic nucleotide-dependent protein kinase appeared to be involved in eIF-4E phosphorylation in B cells, based on the observations that the metabolic labeling of eIF-4E by 32P(i) was insensitive to the protein kinase inhibitors H-7 and HA1004, and that maximal labeling occurred after protein kinase C activity was 'down-regulated' to very low levels in phorbol 12-myristate 13-acetate/ionomycin-activated cells. Dephosphorylation in vivo was blocked by okadaic acid (IC50 = 200 nM). These results indicate that a rapid phosphorylation-dephosphorylation of eIF-4E is associated with high translation rates during the activation of B cells, and implicate protein phosphatase-1 (or possibly -2A) in the dephosphorylation of the initiation factor.

Original languageEnglish
Pages (from-to)19467-19471
Number of pages5
JournalJournal of Biological Chemistry
Volume265
Issue number32
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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