Killer cell immunoglobulin-like receptors and human leukocyte antigen C pathway (Homo sapiens)

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Description

The relationship between killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells and human leukocyte antigen C (HLA-C) molecules on trophoblast cells during pregnancy.

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Bibliography

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  1. Tourdot BE, Brenner MK, Keough KC, Holyst T, Newman PJ, Newman DK; ''Immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated inhibitory signaling is regulated by sequential phosphorylation mediated by distinct nonreceptor tyrosine kinases: a case study involving PECAM-1.''; Biochemistry, 2013 PubMed Europe PMC Scholia
  2. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, Bauer J, Hiby SE, Colucci F, Moffett A; ''Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation.''; J Clin Invest, 2013 PubMed Europe PMC Scholia
  3. Sim MJ, Stowell J, Sergeant R, Altmann DM, Long EO, Boyton RJ; ''KIR2DL3 and KIR2DL1 show similar impact on licensing of human NK cells.''; Eur J Immunol, 2016 PubMed Europe PMC Scholia
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  5. Liu HP, Yu MC, Jiang MH, Chen JX, Yan DP, Liu F, Ge BX; ''Association of supervillin with KIR2DL1 regulates the inhibitory signaling of natural killer cells.''; Cell Signal, 2011 PubMed Europe PMC Scholia
  6. Schmoldt A, Benthe HF, Haberland G; ''Digitoxin metabolism by rat liver microsomes.''; Biochem Pharmacol, 1975 PubMed Europe PMC Scholia
  7. Ashouri E, Rajalingam K, Barani S, Farjadian S, Ghaderi A, Rajalingam R; ''Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.''; J Allergy Clin Immunol Pract, 2022 PubMed Europe PMC Scholia
  8. You Y, Stelzl P, Joseph DN, Aldo PB, Maxwell AJ, Dekel N, Liao A, Whirledge S, Mor G; ''TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion.''; Front Immunol, 2021 PubMed Europe PMC Scholia
  9. Kumar S; ''Natural killer cell cytotoxicity and its regulation by inhibitory receptors.''; Immunology, 2018 PubMed Europe PMC Scholia
  10. Chapel A, Garcia-Beltran WF, Hölzemer A, Ziegler M, Lunemann S, Martrus G, Altfeld M; ''''; , PubMed Europe PMC Scholia
  11. Crespo ÂC, Strominger JL, Tilburgs T; ''Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection.''; Proc Natl Acad Sci U S A, 2016 PubMed Europe PMC Scholia
  12. Fionda C, Stabile H, Molfetta R, Kosta A, Peruzzi G, Ruggeri S, Zingoni A, Capuano C, Soriani A, Paolini R, Gismondi A, Cippitelli M, Santoni A; ''Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.''; Eur J Immunol, 2021 PubMed Europe PMC Scholia
  13. Li Y, Zhu H, Klausen C, Peng B, Leung PC; ''Vascular Endothelial Growth Factor-A (VEGF-A) Mediates Activin A-Induced Human Trophoblast Endothelial-Like Tube Formation.''; Endocrinology, 2015 PubMed Europe PMC Scholia
  14. Matalon O, Ben-Shmuel A, Kivelevitz J, Sabag B, Fried S, Joseph N, Noy E, Biber G, Barda-Saad M; ''Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.''; EMBO J, 2018 PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
140397view11:08, 17 August 2025EgonwRemoved duplicate descriptions
140391view11:01, 17 August 2025EgonwRemoved template comments
140381view19:53, 15 August 2025AlexanderPicoOntology Term : 'signaling pathway' added !
140380view19:52, 15 August 2025AlexanderPicoOntology Term : 'natural killer cell' added !
140379view19:51, 15 August 2025AlexanderPicoModified title
140378view19:50, 15 August 2025AlexanderPicoModified description
140377view19:48, 15 August 2025AlexanderPicofixed X placement
140376view19:47, 15 August 2025AlexanderPicoless empty space; better cell labels
139756view10:32, 3 July 2025Johidi2New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CD34GeneProductCD34 (HGNC) CD34(+) cell present in the endometrium or decidua
DAGProteinP17252 (Uniprot-TrEMBL)
DAP12ProteinO43914 (Uniprot-TrEMBL) Contains immunoreceptor tyrosine-based activation motif (ITAM)
FYNProteinP06241 (Uniprot-TrEMBL)
GM-CSFProteinP04141 (Uniprot-TrEMBL)
  • Supports trophoblast growth and vascular remodeling enhancing placentation
  • Transcriptome profiling via microarray
Grb2ProteinP62993 (Uniprot-TrEMBL)
HLA-CProteinP10321 (Uniprot-TrEMBL)
IFN-γProteinP01579 (Uniprot-TrEMBL) Robustly produced following activating KIR engagement; critical for immune modulation and trophoblast invasion
IP3ProteinQ14643 (Uniprot-TrEMBL)
KIR2DL1ProteinP43626 (Uniprot-TrEMBL) Cytoplasmic tail contains ITIM motif
KIR2DL2 ProteinP43627 (Uniprot-TrEMBL)
KIR2DL3ProteinP43628 (Uniprot-TrEMBL)
KIR2DS1ProteinQ14954 (Uniprot-TrEMBL)
LATProteinO43561 (Uniprot-TrEMBL)
MAPK PathwayPathwayWP769 (WikiPathways)
NF-kbPathwayWP4562 (WikiPathways)
PI3K-Akt PathwayPathwayWP4172 (WikiPathways)
PKCProteinQ04759 (Uniprot-TrEMBL)
PLC-γ1ProteinP19174 (Uniprot-TrEMBL)
RAC1ProteinP63000 (Uniprot-TrEMBL)
RasProteinP01112 (Uniprot-TrEMBL)
SHP-1ProteinP29350 (Uniprot-TrEMBL)
SHP-2ProteinP17706 (Uniprot-TrEMBL)
SLP-76ProteinQ13094 (Uniprot-TrEMBL)
SykProteinP43405 (Uniprot-TrEMBL)
TNF-alpha signalingPathwayWP231 (WikiPathways) This pathway details the signaling events initiated by TNF-α, including activation of NF-κB, apoptosis, and inflammatory gene expression. While it is not trophoblast-specific, the pathway covers the core mechanisms by which TNF-α regulates immune responses and cell behavior, which are directly relevant to its roles in immune regulation and inhibition of trophoblast invasion.
TNF-αProteinP01375 (Uniprot-TrEMBL)
  • Via its action on endometrial stromal cells, TNF-α can also indirectly promote trophoblast invasion by creating a supportive inflammatory environment
  • Elevated TNF-α impairs trophoblast migration and invasion
  • This duality highlights the importance of tightly regulated TNF-α signaling for successful implantation and placental development
Type II interferon signalingPathwayWP619 (WikiPathways) The canonical IFN-γ signaling pathway, including JAK/STAT activation and downstream gene regulation. While it does not specifically mention trophoblasts, it shows how IFN-γ can induce gene expression changes leading to apoptosis and immune modulation.
VAV1ProteinP15498 (Uniprot-TrEMBL)
VEGF-APathwayWP3888 (WikiPathways) Supports trophoblast growth and vascular remodeling
VEGFA-VEGFR2 PathwayPathwayWP3888 (WikiPathways) This pathway is critical for EVT function and spiral artery remodeling, and its disruption is linked to pregnancy complications such as preeclampsia and recurrent pregnancy loss

Annotated Interactions

No annotated interactions

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