Conformational Changes in the Cytoplasmic Region of KIR3DL1 upon Interaction with SHP-2

Cheng, Hong; Schwell, Vered; Curtis, Brett; Fazlieva, Ruzaliya; Röder, Heinrich; Campbell, Kerry S.

doi:10.1016/j.str.2019.01.009

Cited by 10 publications

(19 citation statements)

References 59 publications

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“…A broad conformation effect on phosphorylated ITIMs and on the first segment was observed by addition of tandem SH2 domains, thus suggesting possible intra‐molecular interactions. These findings allow a better understanding of inhibitory KIR function …”

Section: Kir Structure and Peptidesmentioning

confidence: 88%

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

Falco

Sivori

Meazza

et al. 2019

HLA

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The Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop was held in Camogli (Genoa, Italy) in October 2018. This congress brought together 113 participants working on KIR field. Fifty‐eight studies have been presented, the majority of which included unpublished data. Thus, KIR workshop, allowing the meeting of people sharing their knowledge and experience in a friendly atmosphere, still represents a special event of fruitful discussion and exchange of novel breakthrough, results, and ideas. In this report, we summarize all the scientific contributions highlighting the most recent advances in KIR field. Forty abstracts presented at the KIR Workshop are published in this issue.

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Section: Kir Structure and Peptidesmentioning

confidence: 88%

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

Falco

Sivori

Meazza

et al. 2019

HLA

View full text Add to dashboard Cite

show abstract

“…Biochemical evidence demonstrated SHP-1 recruitment to the ITIMs in the cytoplasmic portion of these IR, whereas elegant genetic approaches showed its essential function in maintaining NK cell responsiveness (126,127). Notably, SHP-2 has also been shown to interact with NK cell IRs, suggesting a role in these suppressive signals (123,124,128). Through in vivo genetic approaches, we could however rule out a major role for this phosphatase in this pathway (78).…”

Section: Shp-2 and Inhibitory Receptor Signaling In T And Nk Cellsmentioning

confidence: 99%

SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling

2019

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Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain-containing protein tyrosine phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase (ERK) downstream of various growth factor receptors, thereby exerting essential developmental functions. This phosphatase also deploys proto-oncogenic functions and specific inhibitors have recently been developed. With respect to the immune system, the role of SHP-2 in the signaling of cytokines relevant for myelopoiesis and myeloid malignancies has been intensively studied. The function of this phosphatase downstream of cytokines important for lymphocytes is less understood, though multiple lines of evidence suggest its importance. In addition, SHP-2 has been proposed to mediate the suppressive effects of inhibitory receptors (IRs) that sustain a dysfunctional state in anticancer T cells. Molecules involved in IR signaling are of potential pharmaceutical interest as blockade of these inhibitory circuits leads to remarkable clinical benefit. Here, we discuss the dichotomy in the functions ascribed to SHP-2 downstream of cytokine receptors and IRs, with a focus on T and NK lymphocytes. Further, we highlight the importance of broadening our understanding of SHP-2 ′ s relevance in lymphocytes, an essential step to inform on side effects and unanticipated benefits of its therapeutic blockade.

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“…These studies indicate that KIR2DL5 might have a more obvious inhibitory function [ 15 ]. In addition, KIR3DL1 directly binds to SHP-2 through conformational changes in the intracellular region, inhibiting target cell conjugation and cytotoxicity function [ 14 , 27 ].…”

Section: Inhibitory Receptorsmentioning

confidence: 99%

Research Progress on NK Cell Receptors and Their Signaling Pathways

Chen

Lü

Чуров

et al. 2020

Mediators of Inflammation

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Natural killer cells (NK cells) play an important role in innate immunity. NK cells recognize self and nonself depending on the balance of activating receptors and inhibitory receptors. After binding to their ligands, NK cell receptors trigger subsequent signaling conduction and then determine whether NK is activated or inhibited. Furthermore, NK cell response includes cytotoxicity and cytokine release, which is tightly related to the activation of NK cell-activating receptors and the inhibition of inhibitory receptors on the surfaces of NK cells. The expression and function of NK cell surface receptors also alter in virus infection, tumor, and autoimmune diseases and influence the occurrence and development of diseases. So, it is important to understand the mechanism of recognition between NK receptors and their ligands in pathological conditions and the signaling pathways of NK cell receptors. This review mainly summarizes the research progress on NK cell surface receptors and their signal pathways.

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Conformational Changes in the Cytoplasmic Region of KIR3DL1 upon Interaction with SHP-2

Cited by 10 publications

References 59 publications

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling

Research Progress on NK Cell Receptors and Their Signaling Pathways

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