ArticleCirculation research2018
Inositol Polyphosphate Multikinase Inhibits Angiogenesis via Inositol Pentakisphosphate-Induced HIF-1α Degradation.
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Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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19citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 37% of its field
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The role of vascular endothelial growth factor (VEGF) in major depressive disorder: an update meta-analysis.BMC psychiatry · 2026Pooled it
- IPMK at the crossroads of cellular signaling in health and disease.FEBS letters · 2026Review
- Hypoxic microenvironment and pulmonary hypertension.Respiratory research · 2025Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- From Obscurity to Prominence: IPMK's Expanding Role in Cellular Signaling, Physiology, and Disease.Biomolecules · 2025Review
- Kindlin-3 Promotes Angiogenesis via Notch Signalling and Is Crucial for Functional Recovery Postmyocardial Infarction.Journal of cellular and molecular medicine · 2025Article
- FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice.Nature communications · 2024Article
- Nuclear phosphoinositide signaling promotes YAP/TAZ-TEAD transcriptional activity in breast cancer.The EMBO journal · 2024Article
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Combining systems pharmacology, metabolomics, and transcriptomics to reveal the mechanism of Salvia miltiorrhiza-Cortex moutan herb pair for the treatment of ischemic stroke.Frontiers in pharmacology · 2024Article
- Article
- Identification of key pathways, genes and immune cell infiltration in hypoxia of high-altitude acclimatizationFrontiers in genetics · 2023Article
- The Inositol Phosphate System-A Coordinator of Metabolic Adaptability.International journal of molecular sciences · 2022Review
- HSPA12A Stimulates p38/ERK-AP-1 Signaling to Promote Angiogenesis and Is Required for Functional Recovery Postmyocardial Infarction.Oxidative medicine and cellular longevity · 2022Article
- Inositol Polyphosphate Multikinase Signaling: Multifaceted Functions in Health and Disease.Molecules and cells · 2021Review
- HIF-1α Promotes the Metastasis of Esophageal Squamous Cell Carcinoma by Targeting SP1.Journal of Cancer · 2020Article
- Structural analyses of inositol phosphate second messengers bound to signaling effector proteins.Advances in biological regulation · 2020Review
- Inositol polyphosphates promote T cell-independent humoral immunity via the regulation of Bruton's tyrosine kinase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
14 authors at 2 institutions in 3 countries.
Chenglai FuFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Richa TyagiFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Alfred C ChinFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Tomas RojasFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Ruo-Jing LiFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Prasun GuhaFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Isaac A BernsteinFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Feng RaoFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Risheng XuFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Jiyoung Y ChaFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Jing XuFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Adele M SnowmanFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Gregg L SemenzaFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD.
Solomon H SnyderFrom the Solomon H. Snyder Department of Neuroscience (C.F., R.T., A.C.C., T.R., P.G., I.A.B., F.R., R.X., J.Y.C., J.X., A.M.S., S.H.S.), Department of Pharmacology and Molecular Sciences (R.-J.L., S.H.S.), Institute for Cell Engineering (G.L.S.), McKusick-Nathans Institute of Genetic Medicine (G.L.S.), Department of Pediatrics (G.L.S.), Department of Medicine (G.L.S.), Department of Oncology (G.L.S.), Department of Radiation Oncology (G.L.S.), Department of Biological Chemistry (G.L.S.), and Department of Psychiatry and Behavioral Sciences (S.H.S.), Johns Hopkins University School of Medicine, Baltimore, MD. ssnyder@jhmi.edu.
Johns Hopkins University · USUnited States Nuclear Regulatory Commission · US
Funding
NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGSR37MH018501 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SNYDER, SOLOMON H. · 1990 to 2009
$11.5MNEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGSR01MH018501 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SNYDER, SOLOMON H. · 1985 to 2019
$10.8MNIMH NIH HHS R01 MH018501NIMH NIH HHS R37 MH018501
Abstract
rationaleInositol polyphosphate multikinase (IPMK) and its major product inositol pentakisphosphate (IP5) regulate a variety of cellular functions, but their role in vascular biology remains unexplored.
objectiveWe have investigated the role of IPMK in regulating angiogenesis. METHODS AND
resultsDeletion of IPMK in fibroblasts induces angiogenesis in both in vitro and in vivo models. IPMK deletion elicits a substantial increase of VEGF (vascular endothelial growth factor), which mediates the regulation of angiogenesis by IPMK. The regulation of VEGF by IPMK requires its catalytic activity. IPMK is predominantly nuclear and regulates gene transcription. However, IPMK does not apparently serve as a transcription factor for VEGF. HIF (hypoxia-inducible factor)-1α is a major determinant of angiogenesis and induces VEGF transcription. IPMK deletion elicits a major enrichment of HIF-1α protein and thus VEGF. HIF-1α is constitutively ubiquitinated by pVHL (von Hippel-Lindau protein) followed by proteasomal degradation under normal conditions. However, HIF-1α is not recognized and ubiquitinated by pVHL in
conclusionsIPMK, via its product IP5, negatively regulates angiogenesis by inhibiting VEGF expression. IP5 acts by enhancing HIF-1α hydroxylation and thus pVHL-dependent degradation of HIF-1α.
Indexed as
AnimalsBlood-Brain BarrierCells, CulturedCoculture TechniquesCulture Media, ConditionedFibroblastsGene Expression RegulationGene Knockout TechniquesHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsHypoxia-Inducible Factor 1, alpha SubunitInositol PhosphatesMaleMiceMice, Inbred C57BLCulture Media, ConditionedHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunitinositol pentaphosphateInositol Phosphatesinositol polyphosphate multikinasePhosphotransferases (Alcohol Group Acceptor)RNA, Small InterferingVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVHL protein, mouseVon Hippel-Lindau Tumor Suppressor Proteinblood–brain barrierEgln1 proteinhydroxylationinositol phosphatesvascular endothelial growth factor Avon Hippel-Lindau protein
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