Ljubljana, Slovenia 2006/Terms & References

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Terms

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

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

Dominant negative protein</dt>
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>

ERK kinases</dt>
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.The kinase has to be phosphorylated to become active.</dd>

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

HEK293</dt>
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>

LPS</dt>
LPS stands for lipopolysaccharide. It is a characteristic component of the outer cell membrane in Gram-negative bacteria. It is also an endotoxin and induces a strong immune response in 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>

MD2</dt>
MD2 is an essential protein component of TLR4/MD-2 receptor that binds LPS and thus activates TLR4.</dd>

MyD88</dt>
A central protein of the TLR signaling pathway that transfers signal from TLR receptor to downstream proteins (IRAK4) resulting in the NFκB activation. MyD88 is composed of TIR domain, which 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. Due to the lack of a death domain dnMyD88 does not support the cell signaling.</dd>

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

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

PEST sequence</dt>
A sequence that has been associated with rapidly degraded proteins. The short life-time of a protein is signaled by a region rich in aminoacids proline (P); glutamic acid (E); serine (S); or threonine (T).</dd>

TLR 4</dt>
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>

TRAF6</dt>
A protein that functions as a signaling mediator. It binds to IRAK1 and transfers signal downstream also resulting in NF-κB activation.</dd>

References

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

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

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

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.

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.

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

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

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

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.


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