Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes.

Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes.

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Casitas B-lineage lymphoma-b (Cbl-b) is a ubiquitin ligase (E3) that modulates signaling by tagging molecules for degradation.It is a complex protein with multiple domains and binding partners that are not involved in ubiquitinating substrates.Herein, we demonstrate that Cbl-b, but not c-Cbl, is recruited to the clustered B cell antigen receptor (BCR) and that Cbl-b is required for entry of endocytosed BCRs into late endosomes.The E3 activity of Cbl-b is not lorenametaute.com necessary for BCR endocytic trafficking.

Rather, the ubiquitin associated (UBA) domain is required.Furthermore, the Cbl-b UBA domain is sufficient to confer the receptor trafficking functions of Cbl-b on c-Cbl.Cbl-b is also required for entry of the Toll-like receptor 9 (TLR9) orange zinger tomato into late endosomes and for the in vitro activation of TLR9 by BCR-captured ligands.These data indicate that Cbl-b acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9.