Defective MyD88 does not oligomerize within the activated TLR2/4 complex

Stable Identifier
R-HSA-5602383
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Neisseria meningitidis serogroup B, Chlamydia trachomatis
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

All TLRs, except for TLR3, employ the MyD88-dependent signaling pathway. Autosomal recessive MyD88 deficiency predispose affected patients to recurrent pyogenic bacterial infection due to abolished TLR-mediated cytokine responses of the blood cells (von Bernuth H et al. 2008; Currie AJ et al. 2004). Here we describe several natural loss-of-function MyD88 variants (E52del, L93P, E65del, S34T) that showed severely reduced NFkB activation in human cell-based assays due to reduced homooligomerization and IRAK4 interaction, the two crucial events in the assembly of the Myddosome complex (George J et al. 2011; Nagpal K et al. 2011; Yamamoto T et al. 2014).

Literature References
PubMed ID Title Journal Year
20966070 Two human MYD88 variants, S34Y and R98C, interfere with MyD88-IRAK4-myddosome assembly

George, J, Motshwene, PG, Wang, H, Kubarenko, AV, Rautanen, A, Mills, TC, Hill, AV, Gay, NJ, Weber, AN

J. Biol. Chem. 2011
24316379 Functional assessment of the mutational effects of human IRAK4 and MyD88 genes

Yamamoto, T, Tsutsumi, N, Tochio, H, Ohnishi, H, Kubota, K, Kato, Z, Shirakawa, M, Kondo, N

Mol. Immunol. 2014
18669862 Pyogenic bacterial infections in humans with MyD88 deficiency

von Bernuth, H, Picard, C, Jin, Z, Pankla, R, Xiao, H, Ku, CL, Chrabieh, M, Mustapha, IB, Ghandil, P, Camcioglu, Y, Vasconcelos, J, Sirvent, N, Guedes, M, Vitor, AB, Herrero-Mata, MJ, Aróstegui, JI, Rodrigo, C, Alsina, L, Ruiz-Ortiz, E, Juan, M, Fortuny, C, Yagüe, J, Antón, J, Pascal, M, Chang, HH, Janniere, L, Rose, Y, Garty, BZ, Chapel, H, Issekutz, A, Maródi, L, Rodriguez-Gallego, C, Banchereau, J, Abel, L, Li, X, Chaussabel, D, Puel, A, Casanova, JL

Science 2008
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
primary immunodeficiency disease 612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
Authored
Reviewed
Created
Cite Us!