Evidence map›Paper›PMID 41976321›Full record

ArticleCancers2026

The NKp44-1 Isoform Is an Activating Receptor for PDGF-DD Expressed on Natural Killer Cells.

Alexander J Sedgwick, Md Abdullah Al Kamran Khan, Stephanie Thuy Duong Pham, Melissa A Edeling, Alexandra J Corbett, Julian P Vivian, Yaseelan Palarasah, Alexander D Barrow

Abstract read
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

8 authors.

Alexander J SedgwickDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.ORCID 0000-0002-8200-8967
Md Abdullah Al Kamran KhanDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.ORCID 0000-0002-3484-6333
Stephanie Thuy Duong PhamDepartment of Molecular Medicine, Cancer and Inflammation, University of Southern Denmark, 5000 Odense, Denmark.ORCID 0000-0003-3083-5976
Melissa A EdelingDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.ORCID 0000-0002-8672-8339
Alexandra J CorbettDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.ORCID 0000-0003-1618-4337
Julian P VivianSt. Vincent's Institute of Medical Research, Melbourne, VIC 3065, Australia.
Yaseelan PalarasahDepartment of Molecular Medicine, Cancer and Inflammation, University of Southern Denmark, 5000 Odense, Denmark.ORCID 0000-0002-9337-0232
Alexander D BarrowDepartment of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

Funding

Medical Research Future Fund APP1162217
6 · The paper itself

Abstract

BACKGROUND/

objectivesNatural killer (NK) cells are key innate lymphoid cells that restrict tumour progression by secreting proinflammatory cytokines and directly lysing malignant cells, with their activity tightly regulated by a balance of activating and inhibitory surface receptors. The natural cytotoxicity receptor NKp44 is induced on NK cells following stimulation with IL-2 or IL-15 and recognizes platelet-derived growth factor D (PDGF-DD) as a ligand. Mechanistic interpretation of NKp44 signalling upon PDGF-DD engagement is confounded by the existence of three distinct NKp44 isoforms (NKp44-1, -2, and -3), each capable of initiating divergent intracellular signalling cascades. Unlike NKp44-2 and -3, NKp44-1 encodes a cytoplasmic tyrosine residue (Y238) that conforms to a putative immunoreceptor tyrosine-based inhibition motif (ITIM) and has been reported to suppress NK cell effector functions in some contexts. However, it remains unclear whether the NKp44 isoforms are translated and expressed in NK cells, and formal evidence defining NKp44-1 signalling in response to engagement by PDGF-DD is lacking.

methodsIn this study, we used C-terminal targeting monoclonal antibodies (mAbs) and a NFAT-GFP reporter system to define the expression and signalling properties of NKp44 isoforms in response to PDGF-DD.

resultsWe demonstrate protein expression of NKp44-1 and NKp44-2-/3 receptors in IL-2 expanded NK cells. We further show that NKp44-1 transduces activating rather than inhibitory signals when engaged by PDGF-DD ligand, albeit weaker than NKp44-3. Intriguingly, we find that Y238 is dispensable for NKp44-1 activating signalling and instead functions as a YXXΦ internalisation motif.

conclusionsCollectively, these findings provide the first evidence that the NKp44-1 and NKp44-2/3 isoforms are expressed in NK cells and establish that PDGF-DD activates signalling through NKp44-1 independently of Y238. This work lays the foundations for future studies investigating how PDGF-DD sensing by the different NKp44 isoforms shapes immune functions in different physiological and pathological contexts.

Indexed as

endocytosisimmunoreceptor tyrosine-based inhibition motifnatural killer cellsNKp44platelet-derived growth factor D

Identifiers

PMID41976321
PMCPMC13072323

What Socratic holds

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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 Socratic graph.