Defective MyD88 does not oligomerize within the complex of activated TLR5

Stable Identifier
R-HSA-5602316
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Escherichia coli
Compartment
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TLR5 employs the MyD88-dependent signaling pathway. An autosomal recessive MyD88 deficiency predisposes 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
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
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
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
primary immunodeficiency disease 612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
Authored
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