Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation

Biol Chem. 2012 Mar;393(3):149-60. doi: 10.1515/hsz-2011-0209.

Abstract

Human inositol phosphate multikinase (IPMK) is a multifunctional protein in cellular signal transduction, namely, a multispecific inositol phosphate kinase, phosphatidylinositol 3-kinase, and a scaffold within the mTOR-raptor complex. To fulfill these nuclear and cytoplasmic functions, intracellular targeting of IPMK needs to be regulated. We show here that IPMK, which has been considered to be a preferentially nuclear protein, is a nucleocytoplasmic shuttling protein, whose nuclear export is mediated by classical nuclear export receptor CRM1. We identified a functional nuclear export signal (NES) additionally to its previously described nuclear import signal (NLS). Furthermore, we describe a mechanism by which the activity of the IPMK-NLS is controlled. Protein kinase CK2 binds endogenous IPMK and phosphorylates it at serine 284. Interestingly, this phosphorylation can decrease nuclear localization of IPMK cell type specifically. A controlled nuclear import of IPMK may direct its actions either toward nuclear inositol phosphate (InsPx) metabolism or cytoplasmic actions on InsPx, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P₂], as well as mTOR-raptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Casein Kinase II / metabolism*
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoplasm / metabolism
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Sorting Signals
  • Sequence Alignment

Substances

  • Protein Sorting Signals
  • Phosphotransferases (Alcohol Group Acceptor)
  • inositol polyphosphate multikinase
  • Casein Kinase II
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2