Ljubljana, Slovenia 2006/Terms & References

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<h1>Terms</h1>

<dl><dt>''CpG''</dt>
<dd>Unmethylated CpG motifs usually present in bacterial DNA. They are recognised by TLR9 receptor.</dd>

<dt>''dnMyD88''</dt>
<dd>Dominant negative form of MyD88, which has only TIR-domain.</dd>

<dt>''Dominant negative protein''</dt> 
<dd>A protein that is mutated in a way to compete with wild type protein, but does not support the cascade of additional interactions downstream. This results in a blocking of the pathway.</dd>

<dt>''ERK kinases''</dt>
<dd>Extracellular signal-regulated kinases (ERKs) are regulatory proteins that mediate cell survival, proliferation and differentiation. Activation of ERK is coupled to stimulation of cell-surface proteins via several different upstream signaling pathways, and contributes to the regulation of diverse cellular processes - from cell excitability to gene expression.</dd>

<dt>''Flagellin''</dt>
<dd>This protein can be found in bacterial flagellae. It arranges itself in a hollow cylinder to form the filament in bacterial flagellum.</dd>

<dt>''HEK293''</dt>
<dd>Human embryonic kidney epithelial cell line, that was generated by transformation of human embryonic kidney cell cultures (hence HEK) with sheared adenovirus 5 DNA. They are very easy to work with, and so are a widely-used cell line in cell biology research.</dd>

<dt>''LPS''</dt>
<dd>LPS stands for lipopolysaccharide. It is a characteristic component of the cell membrane of Gram-negative bacteria. It is also an endotoxin, and induces a strong response from normal animal/human immune systems. It binds to the TLR4/MD2/CD14 receptor complex, which promotes the secretion of pro-inflammatory cytokines in many cell types.</dd>

<dt>''MD2''</dt>
<dd>MD2 is an essential protein component that stabilizes TLR4. It has a critical role LPS linking to the LPS receptor.</dd>

<dt>''MyD88''</dt>
<dd>A central protein of the TLR signaling pathway that transfers signal from TLR receptor to downstream proteins (IRAK4) resulting in the NF&kappa;B activation. MyD88 is composed of TIR domain, with which it interacts with TIR domains of TLRs and of a death domain, which interacts with heteromeric death domains of IRAK kinases. Truncated MyD88, comprising only of TIR domain has a dominant-negative phenotype (dnMyD88), because it interacts with cytoplasmic domain of TLRs and competes with wild type MyD88. Because of the lack of a death domain dnMyD88 does not support the cell signaling.</dd>

<dt>''NF-&kappa;B''</dt>
<dd>A transcription factor that functions as heterodimer. NF-&kappa;B dimers are usually sequestered in the cytoplasm in an inactive form. Activation of NF-&kappa;B involves phosphorylation and proteolysis of the inhibitory I&kappa;B proteins, release and nuclear translocation of the NF-&kappa;B, which results in activation of NF&kappa;B-dependent transcription.</dd>

<dt>''PAMP''</dt>
<dd>Abbreviation of Pathogen Associated Molecular Pattern. Those molecules (flagellin, LPS, CpG etc.) are characteristic of pathogenic microorganisms and recognition of which triggers imune response.

<dt>''PEST sequence''</dt>
<dd>A sequence that has been associated with rapidly degraded proteins. The short life-time of a protein is signaled by a region rich in the amino acids proline (P); glutamic acid (E); serine (S); or threonine (T).</dd>

<dt>''TLR 4''</dt>
<dd>Member of TLR receptor familiy that is predominantly activated by lipopolysaccharide. It can activate MyD88 dependent and independent way. For activation also MD2 and CD14 accessory molecules are needed. </dd>

<dt>''TRAF6''</dt>
<dd>A protein that functions as a signalling mediator. It binds to IRAK1 and transfers signal downstream, also resulting in NF-&kappa;B activation.</dd></dl>

<h1>References</h1>
<p>Akira, S. and K. Takeda (2004). "Toll-like receptor signalling." Nat Rev Immunol 4(7): 499-511.</p>

<p>Akira, S., M. Yamamoto, et al. (2003). "Role of adapters in Toll-like receptor signalling." Biochem Soc Trans 31(Pt 3): 637-42.</p>

<p>Beutler, B. (2004). "Inferences, questions and possibilities in Toll-like receptor signalling." Nature 430(6996): 257-63.</p>

<p>Cohen, J. (2002). "The immunopathogenesis of sepsis." Nature 420(6917): 885-91.
Dueber, J. E., B. J. Yeh, et al. (2004). "Rewiring cell signaling: the logic and plasticity of eukaryotic protein circuitry." Curr Opin Struct Biol 14(6): 690-9.</p>

<p>Dupraz, P., S. Cottet, et al. (2000). "Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma -mediated induction of nuclear factor kappa B-dependent nitrite production and apoptosis in beta cells." J Biol Chem 275(48): 37672-8.</p>

<p>Li, X., X. Zhao, et al. (1998). "Generation of destabilized green fluorescent protein as a transcription reporter." J Biol Chem 273(52): 34970-5.</p>

<p>Oda, K. and H. Kitano (2006). "A comprehensive map of the toll-like receptor signaling network." Mol Syst Biol 2: 2006 0015.</p>

<p>Selvarajoo, K. (2006). "Discovering differential activation machinery of the Toll-like receptor 4 signaling pathways in MyD88 knockouts." FEBS Lett 580(5): 1457-64.</p>

<p>Smith, K. D. and A. Ozinsky (2002). "Toll-like receptor-5 and the innate immune response to bacterial flagellin." Curr Top Microbiol Immunol 270: 93-108.</p>


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<table cellpadding="10">
<tr><th>[[Ljubljana, Slovenia 2006|Home]]</th>
<th>[[Ljubljana, Slovenia 2006/Background and Signalling Pathway|Background and Signalling Pathway]]</th>
<th>[[Ljubljana, Slovenia 2006/Project & Model|Project & Model]]</th>
<th>[[Ljubljana, Slovenia 2006/Methods|Methods]]</th>
<th>[[Ljubljana, Slovenia 2006/Results & Conclusions|Results & Conclusions]]</th>
<th>[[Ljubljana, Slovenia 2006/Team members|Team members]]</th></tr></table>[[Image:line-si3.jpg]]