The N and C Termini of the Splice Variants of the Human Mitogen-Activated Protein Kinase-Interacting Kinase Mnk2 Determine Activity and Localization

摘要: The cap-binding eukaryotic initiation factor eIF4E is phosphorylated by the mitogen-activated protein (MAP) kinase-interacting kinases (Mnk’s). Three forms of Mnk’s exist in human cells: Mnk1, Mnk2a, and Mnk2b. These last two are derived from same gene alternative splicing and differ only at their C termini. While Mnk2a contains a MAP kinase-binding site this region, Mnk2b lacks such sequence much less readily activated vitro. Expression mammalian cells leads to increased phosphorylation eIF4E, showing that it acts as an kinase vivo. While cytoplasmic, a substantial amount found nucleus. Both enzymes contain stretch basic residues their N termini plays role binding eIF4G functions nuclear localization signal. Binding eIF4G or import appears be regulated terminus Mnk2a. Furthermore, kinase-binding site regulates entry. Within nucleus, certain variants are present nucleus colocalize with promyelocytic leukemia protein PML, which also binds eIF4E.