Phosphorylation of Eukaryotic Protein Synthesis Initiation Factor 4E at Ser-209

Abstract

Cell adhesion mediated by leukocyte integrin CR3 (CD11b/CD18, alpha m beta 2) may be rapidly modulated without changes in receptor number, and transient changes in adhesivity are thought to be driven by reversible alteration of the affinity of CR3 for ligand. Here we measure the binding affinity of CR3 using purified active and inactive receptor and the ligand, C3bi, coupled to alkaline phosphatase. Immobilized, active CR3 bound saturably and with high affinity (12.5 +/- 4.7 nM). In contrast, inactive CR3 exhibited no measurable binding. High affinity binding could be restored by the addition of the activating anti-CR3 monoclonal antibody KIM-127 to inactive CR3. Since the affinity of KIM-127 for active and inactive receptor was identical, it cannot contribute the energy to convert a low affinity receptor into a high affinity receptor. Rather, KIM-127 appears to facilitate binding of C3bi by lowering the activation energy for the shift from an inactive to an active state. These results suggest that CR3-mediated binding and detachment of cells is not driven by a reversible change in affinity but by two mechanistically distinct processes, an energetically neutral activation step for binding and an energy-dependent step that reverses binding of ligand.

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70s6k

“…Besides S6 and 4E-BP1, insulin-induced phosphorylation of eIF4E (45) and dephosphorylation of eEF2 (57) have been recently implicated as potential downstream targets of this pathway. The phosphorylation of eIF4E is thought to be mediated by protein kinase C (29,70). When bound to 4E-BP1, eIF4E does not serve as a substrate for protein kinase C (70).…”

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

“…In some eukaryotic systems, notably the yeast Saccharomyces cerevisiae, rapamycin also inhibits the basal rate of protein synthesis (Barbet et al, 1996), although it is not yet clear whether the same mechanisms are responsible for the e ects of rapamycin in yeast and mammalian cells (Altmann et al, 1997;Thomas and Hall, 1997). Enhancement of protein synthesis at the translational level by mitogens is also associated with the increased phosphorylation of eIF4E at position Ser 209 (Joshi et al, 1995;Flynn and Proud, 1995), as well as the phosphorylation of eIF4G itself (Morley and Pain, 1995a,b).…”

Paclitaxel induces the phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 through a Cdk1-dependent mechanism

“…eIF-4E is phosphorylated on Ser-209 (Joshi et al,1995), which increases its affinity for the cap structure, enhancing cap-dependent translation (Minich et al, 1994), although this concept has been challenged by a recent study (Scheper et al, 2002). eIF-4E activity is also a function of protein levels.…”