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

TY - JOUR

T1 - Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation.

AU - Meyer, Rüdiger

AU - Nalaskowski, Marcus

AU - Ehm, Patrick

AU - Schröder, Constantin

AU - Naj, Xenia

AU - Brehm, Maria

AU - Mayr, Georg W.

PY - 2012

Y1 - 2012

N2 - 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)P?], as well as mTOR-raptor.

AB - 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)P?], as well as mTOR-raptor.

KW - Humans

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Sequence Alignment

KW - Phosphorylation

KW - Cell Line

KW - Cytoplasm/metabolism

KW - Active Transport, Cell Nucleus

KW - Cell Nucleus/metabolism

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism

KW - Protein Sorting Signals

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - Casein Kinase II/metabolism

KW - Phosphotransferases (Alcohol Group Acceptor)/chemistry/metabolism

KW - Humans

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Sequence Alignment

KW - Phosphorylation

KW - Cell Line

KW - Cytoplasm/metabolism

KW - Active Transport, Cell Nucleus

KW - Cell Nucleus/metabolism

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism

KW - Protein Sorting Signals

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - Casein Kinase II/metabolism

KW - Phosphotransferases (Alcohol Group Acceptor)/chemistry/metabolism

M3 - SCORING: Journal article

VL - 393

SP - 149

EP - 160

JO - BIOL CHEM

JF - BIOL CHEM

SN - 1431-6730

IS - 3

M1 - 3

ER -