DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation

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DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation

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Title: DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation
Author: Rauter, Ingrid; Recher, Mike; Wakim, Rima; Dbaibo, Ghassan; Dasouki, Majed; Barlan, Isil; Baris, Safa; Kutukculer, Necil; Ochs, Hans; Plebani, Alessandro; Kanariou, Maria; Lefranc, Gerard; Reisli, Ismail; Fitzgerald, Katerine; Golenbock, Douglas; Keles, Sevgi; Ceja, Reuben; Jabara, Haifa Halim; McDonald, Douglas Ray; Janssen, Erin Margaret; Massaad, Michel; Ramesh, Narayanaswamy; Borzutzky, Arturo; Benson, Halli Louise; Schneider, Lynda C.; Baxi, Sachin; Notarangelo, Luigi D.; Al-Herz, Waleed; Manis, John P.; Chatila, Talal Amine; Geha, Raif Salim

Note: Order does not necessarily reflect citation order of authors.

Citation: Jabara, Haifa Halim, Douglas Ray McDonald, Erin Margaret Janssen, Michel Massaad, Narayanaswamy Ramesh, Arturo Borzutzky, Ingrid Rauter, et al. 2012. DOCK8 functions as an adaptor that links TLR–MyD88 signaling to B cell activation. Nature immunology 13(6): 612-620.
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Abstract: DOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and \(CD27^+\) memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells.
Published Version: doi:10.1038/ni.2305
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362684/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10610336
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