Inositol Pyrophosphates as Mammalian Cell Signals
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Identification and knockout of their biosynthetic enzymes has shed light on the diverse functions of the inositol pyrophosphates.
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InsP6 can undergo further phosphorylation to form InsP7/8 by InsP6 kinases 1/2/3.
“InsP6 can undergo further phosphorylation to form InsP7/8 by InsP6 kinases 1/2/3 [10].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
The Introduction (page not provided) says the three mammalian IP6 kinases generate 5-IP7 from IP6. It says a different enzyme, PP-IP5K, is primarily responsible for IP8 formation in mammals, so attributing both products to IP6 kinases 1/2/3 overstates the source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the HOIP pathway, IPMK along with ITPK1 plays a crucial role in generating inositol polyphosphates from InsP3.
“In the HOIP pathway (Figure 1B), IPMK, along with Inositol-trisphosphate 3-kinase 1 (ITPK1), plays a crucial role in generating inositol polyphosphates (InsPs) from Inositol 1,4,5-trisphosphate (InsP3) [10,16].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
The Inositol Pyrophosphate Metabolism section (page unavailable) says IPMK sequentially converts IP3 to IP5 and IP3K converts IP3 to IP4. It does not identify IP3K as ITPK1 or describe a HOIP pathway, so those parts of the attributed claim are not supported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIPMK can use either InsP3 or InsP4 to generate InsP5.
“Hence, IPMK can use either InsP3 or InsP4 to generate InsP5 (Ins 1,3,4,5,6).”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
The HOIP pathway uses InsP3 as a precursor and involves a series of phosphorylation events catalyzed by various kinases.
“The HOIP pathway, which uses InsP3 as a precursor, involves a series of phosphorylation events catalyzed by various kinases [10,11] (Figure 1).”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
IPPK converts InsP5 into InsP6.
“Subsequently, inositol pentakisphosphate 2-kinase (IPPK) converts InsP5 into InsP6 (Ins 1,2,3,4,5,6) [10].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
IPMK can modulate cellular signaling by generating highly phosphorylated inositol phosphates (HOIPs).
“This enzyme can modulate cellular signaling through multiple mechanisms: by generating highly phosphorylated inositol phosphates (HOIPs) [10,12,14], producing phosphatidylinositol 3,4,5-trisphosphate (PIP3) [10,12,14], or even functioning independently of its kinase activity through protein–protein interaction [10,11,12,14].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
IPMK can modulate cellular signaling independently of its kinase activity through protein-protein interaction.
“This enzyme can modulate cellular signaling through multiple mechanisms: by generating highly phosphorylated inositol phosphates (HOIPs) [10,12,14], producing phosphatidylinositol 3,4,5-trisphosphate (PIP3) [10,12,14], or even functioning independently of its kinase activity through protein–protein interaction [10,11,12,14].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
IPMK can modulate cellular signaling by producing phosphatidylinositol 3,4,5-trisphosphate (PIP3).
“This enzyme can modulate cellular signaling through multiple mechanisms: by generating highly phosphorylated inositol phosphates (HOIPs) [10,12,14], producing phosphatidylinositol 3,4,5-trisphosphate (PIP3) [10,12,14], or even functioning independently of its kinase activity through protein–protein interaction [10,11,12,14].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [10]
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Cites
The versatility and universality of calcium signalling
Berridge, M. J., Lipp, P., & Bootman, M. D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036035 · Cited by 5,701 · see citing works
Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese Mice
Izumiya, Y., Hopkins, T., Morris, C., Sato, K., Zeng, L., Viereck, J., Hamilton, J. A., Ouchi, N., LeBrasseur, N. K., & Walsh, K. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.003 · Cited by 395 · see citing works
A Role for Nuclear Inositol 1,4,5-Trisphosphate Kinase in Transcriptional Control
Odom, A. R., Stahlberg, A., Wente, S. R., & York, J. D. (2000) · Science · doi:10.1126/science.287.5460.2026 · Cited by 394 · see citing works
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Cited by
Sorted by citations
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
“This enzyme can modulate cellular signaling through multiple mechanisms: by generating highly phosphorylated inositol phosphates (HOIPs) [10,12,14], producing phosphatidylinositol 3,4,5-trisphosphate (PIP3) [10,12,14], or even functioning independently of its kinase activity through protein–protein…”
Influential
- Authors
- Chakraborty, A., Kim, S., & Snyder, S. H.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Snyder, Solomon H.
- Venue
- Science Signaling
- Published
- 2011-08-30
- Volume
- 4
- Issue
- 188
- Pages
- re1-re1
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC3667551
- OpenAlex
- W2053940277
- Cited by
- 160
- References
- 3
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 22 · 2020: 15 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 15 · 2015: 16 · 2014: 9 · 2013: 12 · 2012: 14
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH018501, R37MH018501, MH-18501)
- National Institute on Drug Abuse (P50DA000266, DA000266)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- inositol pyrophosphates, phytic acid, inositol polyphosphate multikinase, IP6K1, Akt signaling, insulin secretion, apoptosis, p53, phosphatidylinositol 3-kinase, inositol phosphate signaling, obesity, Dictyostelium, knockout mice
- MeSH terms
- Animals, Carbohydrate Sequence, Homeostasis, Humans, Inositol Phosphates, Insulin, Molecular Sequence Data, Phenotype, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Mice
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