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MYD88

From Wikipedia, the free encyclopedia

Not to be confused withMyoD.
MYD88
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesMYD88,MYD88D, myeloid differentiation primary response 88, innate immune signal transduction adaptor, MYD88 innate immune signal transduction adaptor, IMD68
External IDsOMIM:602170;MGI:108005;HomoloGene:1849;GeneCards:MYD88;OMA:MYD88 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4615

17874

Ensembl

ENSG00000172936

ENSMUSG00000032508

UniProt

Q99836

P22366

RefSeq (mRNA)

NM_010851

RefSeq (protein)

NP_034981

Location (UCSC)Chr 3: 38.14 – 38.14 MbChr 9: 119.17 – 119.17 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Myeloid differentiation primary response 88 (MYD88)is aproteinthat, in humans, is encoded by theMYD88gene.[5][6]originally discovered in the laboratory of Dan A. Liebermann (Lord et al. Oncogene 1990) as a Myeloid differentiation primary response gene.

Function

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The MYD88 gene provides instructions for making a protein involved in signaling within immune cells. The MyD88 protein acts as anadapter,connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell.

Ininnate immunity,the MyD88 plays a pivotal role in immune cell activation throughToll-like receptors(TLRs), which belong to large group ofpattern recognition receptors(PRR). In general, these receptors sense common patterns which are shared by various pathogens –Pathogen-associated molecular pattern(PAMPs), or which are produced/released during cellular damage –damage-associated molecular patterns(DAMPs).[7]

TLRsare homologous to Toll receptors, which were first described in the onthogenesis of fruit fliesDrosophila,being responsible for dorso-ventral development. Hence,TLRshave been proved in all animals from insects to mammals. TLRs are located either on the cellular surface (TLR1,TLR2,TLR4,TLR5,TLR6) or withinendosomes(TLR3,TLR7,TLR8,TLR9) sensing extracellular or phagocytosed pathogens, respectively. TLRs are integral membrane glycoproteins with typical semicircular-shaped extracellular parts containing leucine-rich repeats responsible for ligand binding, and Intracellular parts containingToll-Interleukin receptor(TIR) domain.[8]

After ligand binding, all TLRs, apart fromTLR3,interact with adaptor protein MyD88. Another adaptor protein, which is activated by TLR3 and TLR4, is calledTIR domain-containing adapter-inducing IFN-β(TRIF). Subsequently, these proteins activate two important transcription factors:

  • NF-κBis a dimeric protein responsible for expression of various inflammatory cytokines, chemokines and adhesion and costimulatory molecules, which in turn triggers acute inflammation and stimulation of adaptive immunity
  • IRFsis a group of proteins responsible for expression of type I interferons setting the so-called antiviral state of a cell.

TLR7andTLR9activate both NF-κB and IRF3 through MyD88-dependent and TRIF-independent pathway, respectively.[8]

The humanorthologMYD88 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 fewpyogenicbacterial infections, demonstrating a major difference between mouse and human immune responses.[9]Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype ofdiffuse large B-cell lymphoma[10]andWaldenström's macroglobulinemia.[11]

Interactions

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Myd88 has been shown tointeractwith:

Gene polymorphisms

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Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified. and for some of them an association with susceptibility to various infectious diseases[22]and to some autoimmune diseases likeulcerative colitiswas found.[23]

References

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  1. ^abcGRCh38: Ensembl release 89: ENSG00000172936–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000032508–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^"Entrez Gene: MYD88 Myeloid differentiation primary response gene (88)".
  6. ^Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE (January 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.PMID9013863.S2CID44843127.
  7. ^Deguine J, Barton GM (2014-11-04)."MyD88: a central player in innate immune signaling".F1000Prime Reports.6:97.doi:10.12703/P6-97.PMC4229726.PMID25580251.
  8. ^abAbbas A, Lichtman AH, Pillai S (10 March 2017).Cellular and molecular immunology(Ninth ed.). Philadelphia, PA.ISBN978-0-323-52323-3.OCLC973917896.{{cite book}}:CS1 maint: location missing publisher (link)
  9. ^von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, et al. (August 2008)."Pyogenic bacterial infections in humans with MyD88 deficiency".Science.321(5889): 691–6.Bibcode:2008Sci...321..691V.doi:10.1126/science.1158298.PMC2688396.PMID18669862.
  10. ^Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, et al. (February 2011)."Oncogenically active MYD88 mutations in human lymphoma".Nature.470(7332): 115–9.Bibcode:2011Natur.470..115N.doi:10.1038/nature09671.PMC5024568.PMID21179087.
  11. ^Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. (August 2012)."MYD88 L265P somatic mutation in Waldenström's macroglobulinemia".The New England Journal of Medicine.367(9): 826–33.doi:10.1056/NEJMoa1200710.PMID22931316.
  12. ^abcFitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, et al. (September 2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction".Nature.413(6851): 78–83.Bibcode:2001Natur.413...78F.doi:10.1038/35092578.PMID11544529.S2CID4333764.
  13. ^abWesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (July 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.doi:10.1074/jbc.274.27.19403.PMID10383454.
  14. ^Chen BC, Wu WT, Ho FM, Lin WW (July 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.PMID11976320.
  15. ^Li S, Strelow A, Fontana EJ, Wesche H (April 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.Bibcode:2002PNAS...99.5567L.doi:10.1073/pnas.082100399.PMC122810.PMID11960013.
  16. ^abMuzio M, Ni J, Feng P, Dixit VM (November 1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling".Science.278(5343): 1612–5.Bibcode:1997Sci...278.1612M.doi:10.1126/science.278.5343.1612.PMID9374458.
  17. ^Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. (June 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.PMID10854325.S2CID32036101.
  18. ^Jefferies C, Bowie A, Brady G, Cooke EL, Li X, O'Neill LA (July 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.PMC87113.PMID11416133.
  19. ^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.PMID15107846.S2CID39773935.
  20. ^Doyle SE, O'Connell R, Vaidya SA, Chow EK, Yee K, Cheng G (April 2003)."Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4".Journal of Immunology.170(7): 3565–71.doi:10.4049/jimmunol.170.7.3565.PMID12646618.
  21. ^Rhee SH, Hwang D (November 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.PMID10952994.
  22. ^Netea MG, Wijmenga C, O'Neill LA (May 2012). "Genetic variation in Toll-like receptors and disease susceptibility".Nature Immunology.13(6): 535–42.doi:10.1038/ni.2284.PMID22610250.S2CID24438756.
  23. ^Matsunaga K, Tahara T, Shiroeda H, Otsuka T, Nakamura M, Shimasaki T, et al. (January 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.PMID24189845.

Further reading

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