ArticleBlood2013
Inositol tetrakisphosphate limits NK cell effector functions by controlling PI3K signaling.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- NK cell-related genes-driven novel molecular subtyping and prognostic signatures for Wilms tumor: uncovering the therapeutic potential of TGX-221 and biomarker role of HS2ST1.Frontiers in oncology · 2025Article
- Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.Cell death & disease · 2024Article
- Evidence that inositol 1,4,5-trisphosphate 3-kinase and inositol 1,3,4,5-tetrakisphosphate are negative regulators of platelet function.Research and practice in thrombosis and haemostasis · 2024Article
- Excitable networks controlling cell migration during development and disease.Seminars in cell & developmental biology · 2020Review
- Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections.PLoS pathogens · 2018Article
- Regulation of Hematopoietic Cell Development and Function Through Phosphoinositides.Frontiers in immunology · 2018Review
- The Interplay between Calmodulin and Membrane Interactions with the Pleckstrin Homology Domain of Akt.The Journal of biological chemistry · 2017Article
- Article
- Impact of dietary components on NK and Treg cell function for cancer prevention.Molecular carcinogenesis · 2015Review
- Article
- Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils.EMBO reports · 2015Review
- hCD2-iCre and Vav-iCre mediated gene recombination patterns in murine hematopoietic cells.PloS one · 2015Article
- Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes.Frontiers in immunology · 2015Review
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells have important functions in cancer immunosurveillance, BM allograft rejection, fighting infections, tissue homeostasis, and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or up-regulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKRs), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP(3) generation by PI3K and generation of diacylglycerol and IP(3) by phospholipase-Cγ (PLCγ). In the present study, we identify a novel role for the phosphorylated IP(3) metabolite inositol (1,3,4,5)tetrakisphosphate (IP(4)) in NK cells. IP(4) promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in mature NK cells, IP(4) limits NKR-induced IFNγ secretion, granule exocytosis, and target-cell killing, in part by inhibiting the PIP(3) effector-kinase Akt. This identifies IP(4) as an important novel regulator of NK cell development and function and expands our understanding of the therapeutically important mechanisms dampening NK cell responses. Our results further suggest that PI3K regulation by soluble IP(4) is a broadly important signaling paradigm.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.