Protein kinase B phosphorylates AHNAK and regulates its subcellular localization

AHNAK is a ubiquitously expressed giant phosphoprotein that was initially i dentified as a gene product subject to transcriptional repression in neurob lastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin, b ut is cytoplasmic or associated with plasma membrane in epithelial cells. I n this study we show that the extranuclear localization of AHNAK in epithel ial cells depends on the formation of cell-cell contacts. We show that AHNA K is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear exclusion of AHNAK is mediated through a nuclear export signa l (NES) in a manner that depends on the phosphorylation of serine 5535 of A HNAK by PKB, a process that also plays a major role in determining extranuc lear localization of AHNAK. AHNAK is a new PKB substrate whose function, th ough unknown, is likely to be regulated by its localization, which is in tu rn regulated by PKB.