Gastric inhibitory polypeptide (GIP), also known as the glucose-dependent insulinotropic peptide is a member of the secretin family of hormones. GIP, together with glucagon-like peptide-1 (GLP-1), belongs to the group of metabolic hormones called incretins that stimulate a decrease in blood glucose levels. GIP is derived from a 153-amino acid pro-protein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. Engagement of Gastric inhibitory polypeptide receptors (GIPR) by GIP on pancreatic beta cells activates adenylate cyclase to regulate insulin compensation in the presence of high circulating glucose.
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF18/AITR/GITR. It has been shown to modulate T lymphocyte survival in peripheral tissues. This cytokine is also found to be expressed in endothelial cells, and is thoμght to be important for interaction between T lymphocytes and endothelial cells.
Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B. Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1.Promotes leukocyte adhesion to endothelial cells .Regulates migration of monocytes from the splenic reservoir to sites of inflammation.
Tumor necrosis factor receptor superfamily member 18(Gitr) contains 3 TNFR-Cys repeats and it have four isforms.IsformA、isformB and isformC is single-pass type I membrane protein and isformD is a secreted protein. The protein is the receptor for TNFSF18.It seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. It mediated NF-kappa-B activation via the TRAF2/NIK pathway.It binds to TRAF1; TRAF2; and TRAF3; but not TRAF5 and TRAF6 and binds through its C-terminus to SIVA1/SIVA.It preferentially expressed in activated T lymphocytes and up-regulated in peripherical mononuclear cells after antigen stimulation/lymphocyte activation.
GITR, also known as TNFRSF18(CD357), belongs to the tumor necrosis factor receptor (TNF-R) superfamily. It is the receptor for TNFSF18. GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. GITR may be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. GITR and its ligand are important costimulatory molecules in the pathogenesis of autoimmune diseases. It also mediates NF-kappa-B activation via the TRAF2/NIK pathway.
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