T Cell Receptor-Induced NF-kB Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-Mediated Calcium Entry

ABSTRACT: T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular calcium (Ca2+) to activate the key transcription factors NFAT and NF-κB. The mechanism of NFAT activation by Ca2+ has been determined; however, the role of Ca2+ in controlling NF-κB signaling is poorly understood and the source of Ca2+ required for NF-κB activation is unknown. We demonstrate that TCR- but not TNF- induced NF-κB signaling upstream of IκB kinase (IKK) activation absolutely requires the influx of extracellular Ca2+ via STIM1-dependent CRAC/Orai channels. We further show that Ca2+ influx controls phosphorylation of the NF-κB protein p65 on Ser536 and that this post- translational modification controls its nuclear localization and transcriptional activation.

ORGANISM(S): Homo sapiens

SUBMITTER: daniel beiting 

PROVIDER: E-GEOD-76804 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress