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Co-inhibition by CTLA4

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-389513

PubChem

R-HSA-389513

Description

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule predominantly expressed on the surface of activated T cells and regulatory T (Treg) cells. It plays a critical role in inhibiting T-cell activation and maintaining immune homeostasis (Alegre et al. 2001). After acctivation of T lymphocytes through their antigen receptor (TCR) induces the upregulation of CTLA-4 expression. CTLA-4 engagement alongside TCR activation inhibits T cell responses through two primary mechanisms: competing with CD28 for B7 binding to reduce costimulation, and delivering a negative signal directly into the T cells. It has been reported that phosphotyrosine-dependent recruitment of the SHP-2 phosphatase to CTLA-4 inhibits T cell activation and expansion by dephosphorylation of CD3/TCR chains.
CTLA-4 inhibits T cell activation through several mechanisms, including the reduction of IL-2 production and expression, as well as by arresting T cells in the G1 phase of the cell cycle (Greenwald et al. 2002). This checkpoint molecule not only impacts the T cells that express it but also exerts a dominant regulatory influence on the proliferation of other T cells. This ability to limit the proliferation of surrounding T cells is crucial in preventing autoreactivity and maintaining immune tolerance, ensuring that the immune system does not inadvertently target the body's own tissues.
Due to its ability to modulate immune responses, CTLA-4 has emerged as a significant therapeutic target for managing conditions such as cancer, autoimmune diseases, and transplant rejection (Tivol et al. 1995, Chambers et al. 1997, Rudd and Schneider 2003).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 10** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P07947	Tyrosine-protein kinase Yes	YES YES1	view
P16410	Cytotoxic T-lymphocyte protein 4	CD152 CTLA4	view
P30153	Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform	PPP2R1A	view
P31749	RAC-alpha serine/threonine-protein kinase	AKT1 PKB RAC	view
P31751	RAC-beta serine/threonine-protein kinase	AKT2	view
P33681	T-lymphocyte activation antigen CD80	CD28LG CD28LG1 CD80 LAB7	view
P42081	T-lymphocyte activation antigen CD86	CD28LG2 CD86	view
Q06124	Tyrosine-protein phosphatase non-receptor type 11	PTP2C PTPN11 SHPTP2	view
Q14738	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform	PPP2R5D	view
Q9Y243	RAC-gamma serine/threonine-protein kinase	AKT3 PKBG	view

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