MyD88-dependent cascade initiated on endosome membrane

Stable Identifier
R-GGA-451477
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Pathway
Species
Gallus gallus
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Chicken TLR21 was demonstrated to use a MyD88-dependent pathway to mediate IL1beta gene expression in HD11 chicken macrophages.(Ciraci C and Lamont SJ 2011) Besides, chTLR21 TIR domain was reported to contain a conserved proline residue at position 844 in its BB-loop (Keestra AM et al 2010), which is critical for activation of MyD88 dependent signaling of hTLR2, hTLR4 and also chTLR5.

Myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays a crucial role in TLR signaling. All TLRs except TLR3 can initiate downstream signaling through MyD88. In the MyD88-dependent pathway, once the adaptor is bound to TLR it leads to recruitment of proteins of the IL1 receptor associated kinase family - IRAK, followed by activation of tumor necrosis factor receptor-associated factor 6 (TRAF6). TRAF6 is an ubiquitin E3 ligase which in turn induces autophosphorylation of TGF-beta activating kinase 1 (TAK1). Activated TAK1 can ultimately mediate the induction of transcription factor NF-kB or mitogen-activated protein kinases (MAPK), such as JNK, p38 and ERK. This results in the translocation of the activated NF-kB and MAPKs to the nucleus and the initiation of appropriate gene transcription leading to the production of many proinflammatory cytokines and antimicrobial peptides.

The chicken MyD88 gene was cloned and its expression was detected in cecum, heart, spleen, liver, kidney, female reproductive tract, thymus and bursa. Over-expression of chicken MyD88 (299aa) significantly stimulated the activation of NF-kB in vitro.

Literature References
PubMed ID Title Journal Year
20498358 Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9

Keestra, AM, de Zoete, MR, Bouwman, LI, van Putten, JP

J Immunol 2010
21095203 Avian-specific TLRs and downstream effector responses to CpG-induction in chicken macrophages

Lamont, SJ, Ciraci, C

Dev Comp Immunol 2011
15804288 Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens

Smith, AL, Boyd, Y, Bumstead, N, Beal, RK, Goodchild, MJ, Young, J, Iqbal, M, Philbin, VJ

Immunology 2005
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