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

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.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Meyer R,Nalaskowski MM,Ehm P,Schröder C,Naj X,Brehm MA,Mayr GW

doi

10.1515/hsz-2011-0209

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

149-60

issue

3

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.2012.393.issue-3/hsz-2011-0209/hsz-2011-02

journal_volume

393

pub_type

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