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 (InsP x) metabolism or cytoplasmic actions on InsP x, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2], as well as mTOR-raptor.
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IPMK is distributed in both the nucleus and the cytoplasm.
“Their work with epifluorescence microscopy suggested that IPMK is distributed in both the nucleus and the cytoplasm.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [45]
IPMK has a known C-terminal nuclear localization signal (NLS).
“Consistent with this, Meyer et al. [45] identified a nuclear export signal (NES, amino acid 170–179) in addition to IPMK’s known C-terminal nuclear localization signal (NLS), suggesting that IPMK may shuttle between these compartments.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [45]
Meyer et al. were the first to investigate IPMK's intracellular distribution in-depth using immunofluorescence analysis of overexpressed N-terminal EYFP-IPMK fusion constructs.
“Meyer et al. [45] were the first to investigate this in-depth, using immunofluorescence analysis of overexpressed N-terminal EYFP-IPMK fusion constructs.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [45]
Meyer et al. identified a nuclear export signal (NES, amino acid 170-179) in IPMK.
“Consistent with this, Meyer et al. [45] identified a nuclear export signal (NES, amino acid 170–179) in addition to IPMK’s known C-terminal nuclear localization signal (NLS), suggesting that IPMK may shuttle between these compartments.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [45]
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From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
- Authors
- Meyer, R., Nalaskowski, M. M., Ehm, P., Schröder, C., Naj, X., Brehm, M. A., & Mayr, G. W.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Nalaskowski, Marcus M.
- Venue
- bchm
- Publisher
- Walter de Gruyter GmbH
- Published
- 2012-03-01
- Volume
- 393
- Issue
- 3
- Pages
- 149-160
- ISSN
- 1431-6730 (ISSN-L)
- 1437-4315
- OpenAlex
- W2333204554
- Cited by
- 21
- References
- 0
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2015: 4 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- nucleocytoplasmic shuttling, CK2 phosphorylation, CRM1 nuclear export, nuclear export signal, nuclear import signal, nuclear localization, phosphatidylinositol 3-kinase, inositol phosphate metabolism, phosphatidylinositol 4,5-bisphosphate
- MeSH terms
- Amino Acid Sequence, Cell Line, Cell Nucleus, Cytoplasm, Humans, Molecular Sequence Data, Phosphorylation, Sequence Alignment, Phosphotransferases (Alcohol Group Acceptor), Cyclic AMP-Dependent Protein Kinases, Protein Sorting Signals, Active Transport, Cell Nucleus, Casein Kinase II, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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