In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 2, No. 76 ( 2009-06-23)
Abstract:
The E3 ubiquitin ligase Casitas B-lineage lymphoma (Cbl-b) is central to antigen-induced immune tolerance and regulates the CD28 dependence of T cell activation. Cbl-b undergoes ubiquitination and proteasomal degradation after adequate costimulation of T cells; however, the mechanism involved is unknown. Here, we identified protein kinase C-θ (PKC-θ) as the critical intermediary for the inactivation of Cbl-b in response to costimulation of T cells through CD28. PKC-θ associated with Cbl-b on stimulation of the T cell receptor. After costimulation of T cells through CD28, Cbl-b was ubiquitinated and degraded through a mechanism that depended on the kinase activity of PKC-θ. Consistent with this mechanism, the impaired responses of PKCθ -deficient T cells were at least partially restored by the concomitant genetic loss of cblb . Thus, our data establish a nonredundant antagonism between PKC-θ and Cbl-b that regulates T cell activation responses.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.2000046
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2009
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