Act 1 Adaptor Protein
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Act 1 Adaptor Protein
Act 1 adaptor protein (Act 1) is an essential intermediate in the interleukin-17 pathway. The IL-17 protein is a pro-inflammatory cytokine important for tissue inflammation in host defense against infection and in autoimmune disease. It is produced by the CD4 + T cells, in particular the Th17 cells. There are 6 subtypes of IL-17, from IL-17A to IL17-F, these subtypes have nearly identical structures. We know that the cytokines are interacting homotypically, but IL-17A and IL-17F are capable do perform heterotypic interaction too. Each cytokine has its own receptor, IL-17RA to IL-17F, and their pathways are still under investigation. It has been proven that these receptors are not using MyD88 and IRAK in their signaling pathways. They indeed use the adaptor Act1 protein, and TRAF family protein in order to activate the ''nuclear factor-kappa B'' (NF-κB), a transcription factor involved in the immunity response (see the pathways explanation below). This protein has different bi ...
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Interleukin 17
Interleukin 17 family (IL17 family) is a family of pro-inflammatory cystine knot cytokines. They are produced by a group of T helper cell known as T helper 17 cell in response to their stimulation with IL-23. Originally, Th17 was identified in 1993 by Rouvier ''et al.'' who isolated IL17A transcript from a rodent T-cell hybridoma. The protein encoded by ''IL17A'' is a founding member of IL-17 family (see below). IL17A protein exhibits a high homology with a viral IL-17-like protein () encoded in the genome of T-lymphotropic rhadinovirus ''Herpesvirus saimiri''. In rodents, IL-17A is often referred to as CTLA8. The biologically active IL-17 interacts with type I cell surface receptor IL-17R. In turn, there are at least three variants of IL-17R referred to as IL17RA, IL17RB, and IL17RC. After binding to the receptor, IL-17 activates several signalling cascades that, in turn, lead to the induction of chemokines. Acting as chemoattractants, these chemokines recruit the immun ...
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Basophil
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from blood into their resident tissues (connective tissue), but they are now known to be different types of cells. Basophils were discovered in 1879 by German physician Paul Ehrlich, who one year earlier had found a cell type present in tissues that he termed ''mastzellen'' (now mast cells). Ehrl ...
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TRAF5
TNF receptor-associated factor 5 is a protein that in humans is encoded by the ''TRAF5'' gene. Function The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Alternate transcriptional splice variants have been characterized. Interactions TRAF5 has been shown to interact with: * ASK1, * CD134, * CD30, * CD40, * RANK * TNFRSF13B, and * TNFRSF14 Herpesvirus entry mediator (HVEM), also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a human cell surface receptor of the T ...
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TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively s ...
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TRAF3
TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus-encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported. Interactions TRAF3 has been shown ...
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C-Jun N-terminal Kinases
c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock. They also play a role in T cell differentiation and the cellular apoptosis pathway. Activation occurs through a dual phosphorylation of threonine (Thr) and tyrosine (Tyr) residues within a Thr-Pro-Tyr motif located in kinase subdomain VIII. Activation is carried out by two MAP kinase kinases, MKK4 and MKK7, and JNK can be inactivated by Ser/Thr and Tyr protein phosphatases. It has been suggested that this signaling pathway contributes to inflammatory responses in mammals and insects. Isoforms The c-Jun N-terminal kinases consist of ten isoforms derived from three genes: JNK1 (four isoforms), JNK2 (four isoforms) and JNK3 (two isofor ...
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CD40 Pathway
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 Monoclonal antibodies, monoclonal antibody that reacted with it) before being named CD4 in 1984. In humans, the CD4 protein is encoded by the ''CD4'' gene. T helper cell, CD4+ T helper cells are leukocytes, white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells. They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 cytotoxic t cell, killer cells, which then destroy the infectious particle. If CD4 cells become depleted, for example in untreated HIV infection, or following immune suppressio ...
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