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Cited by 117Protein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerLipid metabolism and biosynthesis

Direct Modification and Activation of a Nuclear Receptor–PIP 2 Complex by the Inositol Lipid Kinase IPMK

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Blind, Raymond D., Suzawa, Miyuki, Ingraham, Holly A.·2012·Science Signaling
DOI 10.1126/scisignal.2003111PMC PMC3395721
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Abstract

The transcriptional activity of a nuclear receptor is regulated by the phosphorylation status of a bound lipid.

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Crossref · 10.1126/scisignal.2003111

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  • IPMK has roles in nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.

    “Initially identified in yeast and later recognized as essential for mammalian embryonic development, IPMK has transitioned from a niche interest to a focal point in studies of nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [21]

    The Introduction identifies IPMK as required for adaptive transcriptional responses, and the Results report that its activity enhances SF-1-mediated transcription. The References list a yeast study linking IPMK to nuclear mRNA export, but the paper does not establish the claimed roles in nutrient sensing or growth-factor signaling. Page numbers are unavailable in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • IPMK converts PIP2 to PIP3, which is necessary for SF-1-mediated transcriptional activation.

    “IPMK converts PIP2 to PIP3, which is necessary for SF-1-mediated transcriptional activation (Figure 3B).”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [21]

    The Results section, “IPMK Specifically Phosphorylates PIP2 when bound to SF-1” (page unavailable), shows that IPMK converts SF-1-bound PIP2 to PIP3. “Reducing IPMK Activity Impairs SF-1 Transcriptional Activity” reports that IPMK knockdown lowers SF-1 target-gene expression and concludes that PIP3 generation enhances transcription; it does not establish that the conversion is strictly necessary for transcriptional activation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • IPMK knockdown or mutations affecting PIP2 binding to SF-1 disrupt SF-1-mediated transcription.

    “IPKM knockdown or mutations affecting PIP2 binding to SF-1 disrupt this process.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [21]

  • IPMK's PI3K activity is crucial for activating SF-1-mediated transcription.

    “IPMK’s PI3K activity is crucial for activating Steroidogenic factor 1 (SF-1)-mediated transcription [21].”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [21]

  • IPMK functions in mRNA export, chromatin remodeling, transcription, nutrient sensing, and growth factor signaling.

    “Its diverse functions span a wide range of cellular processes, including mRNA export [17,18], chromatin remodeling [19,20], transcription [21,22], nutrient sensing [23], and growth factor signaling [15].”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [21]

    The citation [15] is attached to “growth factor signaling,” so that is the part assessed. The Introduction discusses IPMK’s lipid-kinase activity and transcriptional roles, but neither it nor the passages found by searching for growth factors and Akt states that IPMK functions in growth factor signaling. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Cites

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Authors
Blind, R. D., Suzawa, M., & Ingraham, H. A.
Affiliations
University of California, San Francisco (US)
Corresponding author
Ingraham, Holly A.
ORCID
Venue
Science Signaling
Publisher
American Association for the Advancement of Science (AAAS)
Published
2012-06-19
Volume
5
Issue
229
Pages
ra44-ra44
ISSN
  • 1937-9145 (ISSN-L)
  • 1945-0877
DOI
10.1126/scisignal.2003111
PMC
PMC3395721
OpenAlex
W2060804452
Cited by
117
References
5
Citations by year
2026: 9 · 2025: 19 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 10 · 2016: 6 · 2015: 12 · 2014: 4 · 2013: 12 · 2012: 5
FWCI
4.24
Type
journal article
Language
en
Open access
Locations
  • Science Signaling (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (K12GM081266)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK072246, R01DK072246)
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 › Biochemistry › Lipid metabolism and biosynthesis
Keywords
inositol polyphosphate multikinase, phosphatidylinositol 4,5-bisphosphate, steroidogenic factor 1, phosphatidylinositol 3,4,5-trisphosphate, PTEN, lipid phosphatase, transcriptional activity, phosphatidylinositol 3-kinase
MeSH terms
Binding Sites, Cell Nucleus, Humans, Kinetics, Models, Molecular, Mutation, Phosphorylation, Protein Binding, Substrate Specificity, Blotting, Western, Molecular Structure, Signal Transduction, Protein Structure, Tertiary, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol Phosphates, Phosphatidylinositol 4,5-Diphosphate, Phosphatidylinositol 3-Kinases, RNA Interference, Chromatin Immunoprecipitation, PTEN Phosphohydrolase, Steroidogenic Factor 1, HEK293 Cells

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