The Tec kinase ITK differentially optimizes NFAT, NF-κB, and MAPK signaling during early T cell activation to regulate graded gene induction [preprint]

摘要: The strength of peptide:MHC interactions with the T cell receptor (TCR) is correlated time to first division, relative scale effector response, and graded expression activation-associated proteins like IRF4. To regulate activation programming, TCR proximal kinase ITK simultaneously trigger many biochemically separate signaling cascades. cells lacking exhibit selective impairments in responses after activation, but under strongest conditions activity dispensable. gain insight into whether signal tune observed gene through unequal disparate pathways, we examined Erk1/2 NFAT, NF-{kappa}B translocation naive OT-I CD8+ nuclei. We consistent digital NFAT1 Erk-MAPK, displayed dynamic, response variation was tunable by treatment an inhibitor. Inhibitor-treated showed dampened induction AP-1 factors Fos Fosb, transcripts, survival factor Il2 transcripts. ATAC-seq analysis also revealed genomic regions most sensitive inhibition were enriched for motifs. Specific during peptide stimulation tuned early products c-Fos. Together, these data indicate a key role orchestrating optimal downstream specifically aiding activation. More broadly, mechanism which can produce patterns activated cells.