The mitogen-induced increase in T cell size involves PKC and NFAT activation of Rel/NF-kappaB-dependent c-myc expression.
Cell growth during the G1 stage of the cell cycle is partly controlled by inducing c-myc expression, which in B cells is regulated by the NF-kappaB1 and c-Rel transcription factors. Here, we show that c-myc-dependent growth during T cell activation requires c-Rel and RelA and that blocking this growth by inhibiting protein kinase C theta (PKCtheta) coincides with a failure to upregulate c-myc due to impaired RelA nuclear import and inhibition of NFAT-dependent c-rel transcription. These results demonstrate that different Rel/NF-kappaB dimers regulate the mitogenic growth of mature T and B cells, with a signaling pathway incorporating PKCtheta and NFAT controlling c-Rel/RelA-induced c-myc expression in activated T cells.
Grumont
Raelene
R
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Lock
Peter
P
Mollinari
Michael
M
Shannon
Frances M
FM
Moore
Anna
A
Gerondakis
Steve
S
D000818:Animals; D048429:Cell Size; D004268:DNA-Binding Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011493:Protein Kinase C / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D051996:Transcription Factor RelA; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D008934:Mitogens; C489428:Myc protein, mouse; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; D014157:Transcription Factors; D011493:Protein Kinase C