Interleukin-17 is a potent pro-inflammatory cytokine produced by activated memory T cells. There are at least six members of the IL-17 family in humans and in mice. As IL-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. IL-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.
Interleukin-4 receptor subunit alpha(IL-4RA), alos known as Soluble IL-4 receptor subunit alpha, belongs to the type I cytokine receptor family and type 4 subfamily. It expressed in both Th1 and Th2 cells. It functions as receptor for both interleukin 4 and interleukin 13 and couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and chemokine and mucus production at sites of allergic inflammation. In certain cell types, IL-4RA can signal through activation of insulin receptor substrates, IRS1/IRS2. The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequently it recruits to the complex of the common gamma chain. In immune cells, IL-4RA creates a type I receptor. In non-immune cells, it forms a type II receptor with of IL13RA1. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor and interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP.
Human Lymphocyte activation gene 3 protein( LAG3) is a member of immunoglobulin (Ig) superfamily. LAG3 contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. LAG3 is involved in lymphocyte activation and can bind to HLA class-II antigens. It is selectively expressed in activated T and NK cells. LAG3 has a negative regulatory function in T cells and acts as as a new marker of T cell induced B cell activation. As a soluble molecule, LAG3 activates antigen-presenting cells through MHC class II signaling. It can lead to increased antigen-specific T-cell responses in vivo. LAG-3 has higher affinity to MHC class II than CD4.
Lymphocyte Activating 3(LAG3) belongs to immunoglobulin (Ig) superfamily, Macaca fascicularis LAG3 cDNA encodes 533 amino acids (aa) that include a 17 aa signal sequence, a 451 aa extracellular domain (ECD) with two Ig-like domains, a transmembrane region and a highly charged cytoplasmic region. LAG3's main ligand is MHC class II, to which it binds with higher affinity than CD4. The protein negatively regulates cellular proliferation, activation, and homeostasis of T cells, in a similar fashion to CTLA-4 and PD-1 and has been reported to play a role in Treg suppressive function.
Protein kinase that regulates key processes linked to cell growth and survival. Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics. Regulates DNA repair potentially by activating the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks.
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