Differential expression of nuclear proto-oncogenes in T cells triggered with mitogenic and nonmitogenic T3 and T11 activation signals.
The relationship between induction of nuclear proto-oncogenes and cellular proliferation is not fully understood. To better define this relationship, we have studied c-fos, c-myc, and c-myb mRNA induction in T lymphocytes where early and late activation events have been clearly delineated. In T cells, initial activation from G0 to G1 results from stimulation of either the antigen/major histocompatibility complex receptor (T3-Ti) or the T11 structure; further cycle progression and proliferation follow interaction of interleukin 2 (IL-2) with the IL-2 receptor. These events can be dissected with monoclonal antibodies to T3 or T11 which cause early activation but differ in their ability to initiate IL-2-dependent cycle progression and proliferation. In T lymphocytes triggered through either T3-Ti or T11, c-fos is induced with a nonmitogenic activation signal whereas c-myb is only induced with a mitogenic signal capable of triggering IL-2 and IL-2 receptor expression. Furthermore, c-myc induction is biphasic and associated with both early and late activation events. Early c-myc, like c-fos, is induced with a nonmitogenic signal. In contrast, induction of late c-myc, like that of c-myb, requires a mitogenic signal. Thus, appearance of c-fos and initial c-myc mRNA seem to be early responses to membrane signaling whereas late c-myc and c-myb are more directly associated with actual cellular proliferation. That nonmitogenic stimulation of T cells via T3-Ti not only abrogates T11-mediated proliferation but also eliminates late c-myc and c-myb transcription further supports this notion.
Shipp
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MA
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
Reinherz
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D000954:Antigens, Surface / Q000276:immunology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D017252:CD3 Complex; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D002118:Calcium