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

作者：Meyer Ruediger; Nalaskowski Marcus M^*; Ehm Patrick; Schroeder Constantin; Naj Xenia; Brehm Maria A; Mayr Georg W

来源：Biological Chemistry, 2012, 393(3): 149-160.

DOI：10.1515/hsz-2011-0209

• IPMK
• nuclear export signal
• nuclear import signal
• protein phosphorylation

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 (InsP(x)) metabolism or cytoplasmic actions on InsP(x), phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P-2], as well as mTOR-raptor.

• 出版日期2012-3