MYD88

From Wikipedia, the free encyclopedia
  (Redirected from Myd88)
Jump to: navigation, search
Myeloid differentiation primary response 88
Toll-like receptor pathways revised.jpg
Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MYD88 ; MYD88D
External IDs OMIM602170 MGI108005 HomoloGene1849 ChEMBL: 5919 GeneCards: MYD88 Gene
RNA expression pattern
PBB GE MYD88 209124 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4615 17874
Ensembl ENSG00000172936 ENSMUSG00000032508
UniProt Q99836 P22366
RefSeq (mRNA) NM_001172566 NM_010851
RefSeq (protein) NP_001166037 NP_034981
Location (UCSC) Chr 3:
38.14 – 38.14 Mb
Chr 9:
119.34 – 119.34 Mb
PubMed search [1] [2]

Myeloid differentiation primary response gene 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.[1][2]

Model organisms[edit]

Model organisms have been used in the study of MYD88 function. The gene was originally discovered and cloned by Dan Liebermann and Barbara Hoffman in mice.[3] In that species it is a universal adapter protein as it is used by almost all TLRs (except TLR 3) to activate the transcription factor NF-κB. Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK.[4] It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease.[5]

A conditional knockout mouse line, called Myd88tm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty-one tests were carried out on homozygous mutant animals, revealing one abnormality: male mutants had an increased susceptibility to bacterial infection.

Function[edit]

The human ortholog MYD88 seems to function similarly to mice, since the immunological phenotype of human cells deficient in MYD88 is similar to cells from MyD88 deficient mice. However, available evidence suggests that MYD88 is dispensable for human resistance to common viral infections and to all but a few pyogenic bacterial infections, demonstrating a major difference between mouse and human immune responses.[15] Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of Diffuse Large B-cell Lymphoma[16] and Waldenstrom's Macroglobulinemia.[17]

Interactions[edit]

Myd88 has been shown to interact with:

Gene polymorphisms[edit]

Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified and for some of them an association with susceptibility to various infective disease [28] and also with susceptibility to some autoimmune diseases like ulcerative colitis was found. [29]

References[edit]

  1. ^ "Entrez Gene: MYD88 Myeloid differentiation primary response gene (88)". 
  2. ^ Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE (Jan 1997). "The cloning and characterization of human MyD88: a member of an IL-1 receptor related family". FEBS Letters 402 (1): 81–4. doi:10.1016/S0014-5793(96)01506-2. PMID 9013863. 
  3. ^ Lord KA, Hoffman-Liebermann B, Liebermann DA (Jul 1990). "Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6". Oncogene 5 (7): 1095–7. PMID 2374694. 
  4. ^ Arancibia SA, Beltrán CJ, Aguirre IM, Silva P, Peralta AL, Malinarich F, Hermoso MA (2007). "Toll-like receptors are key participants in innate immune responses". Biological Research 40 (2): 97–112. doi:10.4067/S0716-97602007000200001. PMID 18064347. 
  5. ^ Lim JE, Kou J, Song M, Pattanayak A, Jin J, Lalonde R, Fukuchi K (Sep 2011). "MyD88 deficiency ameliorates β-amyloidosis in an animal model of Alzheimer's disease". The American Journal of Pathology 179 (3): 1095–103. doi:10.1016/j.ajpath.2011.05.045. PMC 3157279. PMID 21763676. 
  6. ^ "Salmonella infection data for Myd88". Wellcome Trust Sanger Institute. 
  7. ^ a b Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  8. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  9. ^ "International Knockout Mouse Consortium". 
  10. ^ "Mouse Genome Informatics". 
  11. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  12. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  13. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  14. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  15. ^ 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 (Aug 2008). "Pyogenic bacterial infections in humans with MyD88 deficiency". Science 321 (5889): 691–6. doi:10.1126/science.1158298. PMC 2688396. PMID 18669862. 
  16. ^ Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature 470 (7332): 115–9. doi:10.1038/nature09671. PMID 21179087. 
  17. ^ Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Sheehy P, Manning RJ, Patterson CJ, Tripsas C, Arcaini L, Pinkus GS, Rodig SJ, Sohani AR, Harris NL, Laramie JM, Skifter DA, Lincoln SE, Hunter ZR (2012). "MYD88 L265P somatic mutation in Waldenström's macroglobulinemia". N. Engl. J. Med. 367 (9): 826–33. doi:10.1056/NEJMoa1200710. PMID 22931316. 
  18. ^ a b c Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, Brint E, Dunne A, Gray P, Harte MT, McMurray D, Smith DE, Sims JE, Bird TA, O'Neill LA (Sep 2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction". Nature 413 (6851): 78–83. doi:10.1038/35092578. PMID 11544529. 
  19. ^ a b Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (Jul 1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". The Journal of Biological Chemistry 274 (27): 19403–10. PMID 10383454. 
  20. ^ Chen BC, Wu WT, Ho FM, Lin WW (Jul 2002). "Inhibition of interleukin-1beta -induced NF-kappa B activation by calcium/calmodulin-dependent protein kinase kinase occurs through Akt activation associated with interleukin-1 receptor-associated kinase phosphorylation and uncoupling of MyD88". The Journal of Biological Chemistry 277 (27): 24169–79. doi:10.1074/jbc.M106014200. PMID 11976320. 
  21. ^ Li S, Strelow A, Fontana EJ, Wesche H (Apr 2002). "IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase". Proceedings of the National Academy of Sciences of the United States of America 99 (8): 5567–72. doi:10.1073/pnas.082100399. PMC 122810. PMID 11960013. 
  22. ^ a b Muzio M, Ni J, Feng P, Dixit VM (Nov 1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science 278 (5343): 1612–5. PMID 9374458. 
  23. ^ Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, Lewis A, Ray K, Tschopp J, Volpe F (Jun 2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nature Cell Biology 2 (6): 346–51. doi:10.1038/35014038. PMID 10854325. 
  24. ^ Jefferies C, Bowie A, Brady G, Cooke EL, Li X, O'Neill LA (Jul 2001). "Transactivation by the p65 subunit of NF-kappaB in response to interleukin-1 (IL-1) involves MyD88, IL-1 receptor-associated kinase 1, TRAF-6, and Rac1". Molecular and Cellular Biology 21 (14): 4544–52. doi:10.1128/MCB.21.14.4544-4552.2001. PMC 87113. PMID 11416133. 
  25. ^ Chuang TH, Ulevitch RJ (May 2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nature Immunology 5 (5): 495–502. doi:10.1038/ni1066. PMID 15107846. 
  26. ^ Doyle SE, O'Connell R, Vaidya SA, Chow EK, Yee K, Cheng G (Apr 2003). "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". Journal of Immunology 170 (7): 3565–71. PMID 12646618. 
  27. ^ Rhee SH, Hwang D (Nov 2000). "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase". The Journal of Biological Chemistry 275 (44): 34035–40. doi:10.1074/jbc.M007386200. PMID 10952994. 
  28. ^ Netea MG, Wijmenga C, O'Neill LA (Jun 2012). "Genetic variation in Toll-like receptors and disease susceptibility". Nature Immunology 13 (6): 535–42. doi:10.1038/ni.2284. PMID 22610250. 
  29. ^ Matsunaga K, Tahara T, Shiroeda H, Otsuka T, Nakamura M, Shimasaki T, Toshikuni N, Kawada N, Shibata T, Arisawa T (Jan 2014). "The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis". Molecular Medicine Reports 9 (1): 28–32. doi:10.3892/mmr.2013.1769. PMID 24189845. 

Further reading[edit]

External links[edit]