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TTRAP
Transforming growth factor-β (TGF-β) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signalling routes are also employed by this pleiotropic cytokine. For instance recently, we have demonstrated that ligand-occupied TGF-β receptors can directly trigger the TRAF6-TAK1 signalling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule TTRAP as a novel component of this non-canonical TGF-β pathway. We show that the protein associates with TGF-β receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-β activated p38 and NF-κB responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-β, suggesting that the protein is an important component of the TGF-β induced apoptotic process. Interactions TTRAP has been shown to interact with ETS1, TNFRSF1B and CD40. References Further reading ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TNFRSF1B
Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain ( DD). Function The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1A. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD40 (protein)
Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects. Deficiency can cause Hyper-IgM syndrome type 3. Function The protein receptor encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ETS1
Protein C-ets-1 is a protein that in humans is encoded by the ''ETS1'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors. Function There are 28 ETS genes in humans and 27 in mice. They bind the DNA via their winged-helix-turn-helix DNA binding motif known as the Ets domain that specifically recognizes DNA sequences that contain a GGAA/T core element. However, Ets proteins differ significantly in their preference for the sequence flanking the GGAA/T core motif. For instance, the consensus sequence for Ets1 is PuCC/a-GGAA/T-GCPy. On the other hand, many natural Ets1-responsive GGAA/T elements differ from this consensus sequence. The later suggests that several other transcription factors may facilitate Ets1 binding to unfavorable DNA sequences. ChIP-Seq studies have shown that Ets1 can bind both AGGAAG and CGGAAG motifs. Ets1 binds to DNA as a monomer. Phosphorylation of serine residues of the C-terminal domain (in the nucleotide sequence ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transforming Growth Factor-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in which it ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SMAD (protein)
Smads (or SMADs) comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the ''Caenorhabditis elegans'' SMA ("small" worm phenotype) and MAD family ("Mothers Against Decapentaplegic") of genes in Drosophila. There are three distinct sub-types of Smads: receptor-regulated Smads ( R-Smads), common partner Smads (Co-Smads), and inhibitory Smads ( I-Smads). The eight members of the Smad family are divided among these three groups. Trimers of two receptor-regulated SMADs and one co-SMAD act as transcription factors that regulate the expression of certain genes. Sub-types The R-Smads consist of Smad1, Smad2, Smad3, Smad5 and Smad8/9, and are involved in direct signaling from the TGF-B receptor. Smad4 is the only known human Co-Smad, and has the role of partneri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Signalling Routes
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] |
Pleiotropic Cytokine
Pleiotropy (from Greek , 'more', and , 'way') occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function. Pleiotropy can arise from several distinct but potentially overlapping mechanisms, such as gene pleiotropy, developmental pleiotropy, and selectional pleiotropy. Gene pleiotropy occurs when a gene product interacts with multiple other proteins or catalyzes multiple reactions. Developmental pleiotropy occurs when mutations have multiple effects on the resulting phenotype. Selectional pleiotropy occurs when the resulting phenotype has many effects on fitness (depending on factors such as age and gender). An example of pleiotropy is phenylketonuria, an inherited d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electron pairs, often through Lewis bases. The nature of metal–ligand bonding can range from covalent to ionic. Furthermore, the metal–ligand bond order can range from one to three. Ligands are viewed as Lewis bases, although rare cases are known to involve Lewis acidic "ligands". Metals and metalloids are bound to ligands in almost all circumstances, although gaseous "naked" metal ions can be generated in a high vacuum. Ligands in a complex dictate the reactivity of the central atom, including ligand substitution rates, the reactivity of the ligands themselves, and redox. Ligand selection requires critical consideration in many practical areas, including bioinorganic and medicinal chemistry, homogeneous catalysis, and environmental chemi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MAP Kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. MAP kinases are found in eukaryotes only, but they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes. MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). Discovery The first mitogen-activated protein kinase to be discovered was ERK1 (MAPK3) in mammals. Since ERK1 and its close relative ERK2 (MAPK1) are both involved in growth factor signaling, the family ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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