Differential regulation of c-Rel translocation in activated B and T cells.
c-Rel induction in activated lymphocytes is suppressed by the immunosuppressive drug, FK506. Here we show that FK506-suppressible, delayed c-Rel induction is similar in B and T cells and is regulated by mRNA production. In contrast, rapid nuclear translocation of pre-existing cytoplasmic c-Rel occurs only in B cells, but not in T cells. Analysis of I-kappaBalpha and -beta in these cells showed that both I-kappaBalpha and I-kappaBbeta were rapidly degraded in response to stimulation in B cells, but only I-kappaBalpha was affected in T cells. These observations suggest that 1) different Rel proteins in the same cell may be sequestered in the cytoplasm differently, 2) the sequestration mechanism is cell-type specific, and 3) differential sensitivities of I-kappaBalpha and beta in B and T cells may regulate, in part, the rapid response of family members. We propose that subunit-specific and cell-specific regulation of nuclear translocation may help determine the varied cellular responses to different stimuli.
Venkataraman
L
L
Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA 02254, USA.
Wang
W
W
Sen
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014157:Transcription Factors; D003513:Cycloheximide; D016559:Tacrolimus