AMP-activated protein kinase up-regulates mitogen-activated protein (MAP) kinaseinteracting serine/threonine kinase 1a-dependent phosphorylation of eukaryotic translation initiation factor 4E

Abstract

AMP-activated protein kinase (AMPK) is a molecular energy sensor that acts to sustain cellular energy balance. Although AMPK is implicated in the regulation of a multitude of ATP-dependent cellular processes, exactly how these processes are controlled by AMPK as well as the identity of AMPK targets and pathways continues to evolve. Here we identify MAP kinaseinteracting serine/threonine protein kinase 1a (MNK1a) as a novel AMPK target. Specifically, we show AMPK-dependent Ser353 phosphorylation of the human MNK1a isoform in cellfree and cellular systems. We show that AMPK and MNK1a physically interact and that in vivo MNK1a-Ser353 phosphorylation requires T-loop phosphorylation, in good agreement with a recently proposed structural regulatory model of MNK1a. Our data suggest a physiological role for MNK1a-Ser353 phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo.