ArticleThe Journal of biological chemistry2007
Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Three phosphatase families form a community: The phosphohydrolases that act upon inositol pyrophosphates.FEBS letters · 2026Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.Plant biotechnology journal · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Protein pyrophosphorylation by inositol phosphates: a novel post-translational modification in plants?Frontiers in plant science · 2024Review
- Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Inositol Pyrophosphate-Controlled Kinetochore Architecture and Mitotic Entry inJournal of fungi (Basel, Switzerland) · 2022Article
- Whole BodyInternational journal of molecular sciences · 2022Article
- Phytate as a Phosphorus Nutrient with Impacts on Iron Stress-Related Gene Expression for Phytoplankton: Insights from the DiatomApplied and environmental microbiology · 2022Article
- Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis.International journal of biological sciences · 2022Article
- The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis.Advances in biological regulation · 2022Article
- Wheat inositol pyrophosphate kinase TaVIH2-3B modulates cell-wall composition and drought tolerance in Arabidopsis.BMC biology · 2021Article
- The Asp1 pyrophosphatase from S. pombe hosts a [2Fe-2S]Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Inositol Pyrophosphate Pathways and Mechanisms: What Can We Learn from Plants?Molecules (Basel, Switzerland) · 2020Review
- Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals.Molecules (Basel, Switzerland) · 2020Review
- Phosphorylation of vaccinia-related kinase 1 at threonine 386 transduces glucose stress signal in human liver cells.Bioscience reports · 2020Article
- Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases.Molecules (Basel, Switzerland) · 2020Review
20 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
Mammalian cells utilize multiple signaling mechanisms to protect against the osmotic stress that accompanies plasma membrane ion transport, solute uptake, and turnover of protein and carbohydrates (Schliess, F., and Haussinger, D. (2002) Biol. Chem. 383, 577-583). Recently, osmotic stress was found to increase synthesis of bisdiphosphoinositol tetrakisphosphate ((PP)2-InsP4), a high energy inositol pyrophosphate (Pesesse, X., Choi, K., Zhang, T., and Shears, S. B. (2004) J. Biol. Chem. 279, 43378-43381). Here, we describe the purification from rat brain of a diphosphoinositol pentakisphosphate kinase (PPIP5K) that synthesizes (PP)2-InsP4. Partial amino acid sequence, obtained by mass spectrometry, matched the sequence of a 160-kDa rat protein containing a putative ATP-grasp kinase domain. BLAST searches uncovered two human isoforms (PPIP5K1 (160 kDa) and PPIP5K2 (138 kDa)). Recombinant human PPIP5K1, expressed in Escherichia coli, was found to phosphorylate diphosphoinositol pentakisphosphate (PP-InsP5) to (PP)2-InsP4 (Vmax = 8.3 nmol/mg of protein/min; Km = 0.34 microM). Overexpression in human embryonic kidney cells of either PPIP5K1 or PPIP5K2 substantially increased levels of (PP)2-InsP4, whereas overexpression of a catalytically dead PPIP5K1(D332A) mutant had no effect. PPIP5K1 and PPIP5K2 were more active against PP-InsP5 than InsP6, both in vitro and in vivo. Analysis by confocal immunofluorescence showed PPIP5K1 to be distributed throughout the cytoplasm but excluded from the nucleus. Immunopurification of overexpressed PPIP5K1 from osmotically stressed HEK cells (0.2 M sorbitol; 30 min) revealed a persistent, 3.9 +/- 0.4-fold activation when compared with control cells. PPIP5Ks are likely to be important signaling enzymes.
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