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Cutting edge: TCR ligation triggers digital activation of NF-kappaB.

ABSTRACT: TCR-mediated activation of the transcription factor NF-?B is required for T cell proliferation, survival, and effector differentiation. Although this pathway is the subject of intense study, it is not known whether TCR signaling to NF-?B is digital (switch-like) or analog in nature. Through analysis of the phosphorylation and degradation of I?B? and the nuclear translocation and phosphorylation of the NF-?B subunit RelA, we show that TCR-directed NF-?B activation is digital. Furthermore, digitization occurs well upstream of the I?B kinase complex, as protein kinase C translocation to the immunologic synapse and activation-associated aggregation of Bcl10 and Malt1 also demonstrate both digital behavior and high correlation with RelA nuclear translocation. Thus, similar to the TCR-to-MAPK signaling cascade, analog Ag inputs are converted to digital activation outputs to NF-?B at an early step downstream of TCR ligation.

SUBMITTER: Kingeter LM

PROVIDER: S-EPMC2950878 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Cutting edge: TCR ligation triggers digital activation of NF-kappaB.

Kingeter Lara M LM Paul Suman S Maynard Sean K SK Cartwright Natalia G NG Schaefer Brian C BC

Journal of immunology (Baltimore, Md. : 1950) 20100920 8

TCR-mediated activation of the transcription factor NF-κB is required for T cell proliferation, survival, and effector differentiation. Although this pathway is the subject of intense study, it is not known whether TCR signaling to NF-κB is digital (switch-like) or analog in nature. Through analysis of the phosphorylation and degradation of IκBα and the nuclear translocation and phosphorylation of the NF-κB subunit RelA, we show that TCR-directed NF-κB activation is digital. Furthermore, digitiz ...[more]

PMID: 20855880

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