DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation
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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
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ni.2305Metadata
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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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362684/pdf/Terms of Use
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