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IRAK4
IRAK-4 (interleukin-1 receptor-associated kinase 4), in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications. Animals without IRAK-4 are more susceptible to viruses and bacteria but completely resistant to LPS challenge. History The first IL-1 receptor-associated kinase (IRAK) was observed in 1994 through experiments with murine T helper cell lines D10N and EL-4. Two years later the first experimental member of this family of kinases, IRAK1, was cloned. In 2002, through database searches at the National Center for Biotechnology Information in an attempt to recognize novel members of the IRAK family ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin-1 Receptor-associated Kinase
The interleukin-1 receptor (IL-1R) associated kinase (IRAK) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. IRAKs are essential components of the Interleukin-1 receptor signaling pathway and some Toll-like receptor signaling pathways. Toll-like receptors (TLRs) detect microorganisms by recognizing specific pathogen-associated molecular patterns (PAMPs) and IL-1R family members respond the interleukin-1 (IL-1) family cytokines. These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily, MyD88.Suzuki, N., Suzuki, S., and Saito, T. 2005. IRAKs: Key Regulatory Kinases of Innate Immunity. Curr. Med. Chem. – Anti-Inflammatory & Anti-Allergy Agents, 4(1), 13-20. This is followed by the activation of IRAKs. TLRs and IL-1R members have a highly conserved amino acid sequence in their cytoplasmic domain called the Toll/Interl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Toll-like Receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in Intracellular receptor, intracellular Vesicle (biology and chemistry), vesicles (because they are sensors of nucleic acids). TLRs received their name from their similarity to th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 1 Family
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on the pathogenesis of fever. The studies were performed by Eli Menkin and Paul Beeson in 1943–1948 on the fever-producing properties of proteins released from rabbit peritoneal exudate cells. These studies were followed by contributions of several investigators, who were primarily interested in the link between fever and infection/inflammation. The basis for the term "interleukin" was to streamline the growing number of biological properties attributed to soluble factors from macrophages and lymphocytes. IL-1 was the name given to the macrophage product, whereas IL-2 was used to define the lymphocyte product. At the time of the assignment of these names, there was no amino acid sequence analysis known and the terms were used to define bi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer membrane of Gram-negative bacteria. Today, the term ''endotoxin'' is often used synonymously with LPS, although there are a few endotoxins (in the original sense of toxins that are inside the bacterial cell that are released when the cell disintegrates) that are not related to LPS, such as the so-called delta endotoxin proteins produced by '' Bacillus thuringiensis''. Lipopolysaccharides can have substantial impacts on human health, primarily through interactions with the immune system. LPS is a potent activator of the immune system and pyrogen (agent that causes fever). In severe cases, LPS can play a role in causing septic shock. In lower levels and over a longer time period, there is evidence LPS may play an important and harmful role ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Signalling Of IRAK4
In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' includes audio, video, speech, image, sonar, and radar as examples of signal. A signal may also be defined as observable change in a quantity over space or time (a time series), even if it does not carry information. In nature, signals can be actions done by an organism to alert other organisms, ranging from the release of plant chemicals to warn nearby plants of a predator, to sounds or motions made by animals to alert other animals of food. Signaling occurs in all organisms even at cellular levels, with cell signaling. Signaling theory, in evolutionary biology, proposes that a substantial driver for evolution is the ability of animals to communicate with each other by developing ways of signaling. In human engineering, signals are typ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AP-1 Transcription Factor
Activator protein 1 (AP-1) is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. AP-1 controls a number of cellular processes including differentiation, proliferation, and apoptosis. The structure of AP-1 is a heterodimer composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. History AP-1 was first discovered as a TPA-activated transcription factor that bound to a cis-regulatory element of the human metallothionein IIa ( hMTIIa) promoter and SV40. The AP-1 binding site was identified as the 12-O-Tetradecanoylphorbol-13-acetate ( TPA) response element (TRE) with the consensus sequence 5’-TGA G/C TCA-3’. The AP-1 subunit Jun was identified as a novel oncoprotein of avian sarcoma virus, and Fos-associated p39 protein was identified as the transcript of the cellular Jun gene. Fos was first isolated as the cellular homologue of two ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAPK/ERK Pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, such as mitogen-activated protein kinases (MAPKs), originally called extracellular signal-regulated kinases (ERKs), which communicate by adding phosphate groups to a neighboring protein ( phosphorylating it), thereby acting as an "on" or "off" switch. When one of the proteins in the pathway is mutated, it can become stuck in the "on" or "off" position, a necessary step in the development of many cancers. In fact, components of the MAPK/ERK pathway were first discovered in cancer cells, and drugs that reverse the "on" or "off" switch are ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IKK2
IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the ''IKBKB'' (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene. Function IKK-β is an enzyme that serves as a protein subunit of IκB kinase, which is a component of the cytokine-activated intracellular signaling pathway involved in triggering immune responses. IKK's activity causes activation of a transcription factor known as Nuclear Transcription factor kappa-B or NF-κB. Activated IKK-β phosphorylates a protein called the '' inhibitor of NF-κB'', IκB (IκBα), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded via the ubiquitination pathway, freeing NF-κB, and allowing its entry into the nucleus of the cell where it activates various genes involved in inflammation and other immune responses. Clinical significance IKK-β plays a significant role in brain cells following a stroke. If NF-κ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IkB Kinase , British engineer
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IKB is an initialism that can refer to * International Klein Blue, a deep blue hue * IκB -kappa-B a protein complex * IKB Deutsche Industriebank, a German bank * Ikebukuro Station, JR East station code * Isambard Kingdom Brunel Isambard Kingdom Brunel (; 9 April 1806 – 15 September 1859) was a British civil engineer who is considered "one of the most ingenious and prolific figures in engineering history," "one of the 19th-century engineering giants," and "on ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TRAF6
TRAF6 is a TRAF human protein. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
