Differential expression of a zinc finger-encoding gene in response to positive versus negative signaling through receptor immunoglobulin in murine B lymphocytes.
Egr-1 is a murine early growth factor-inducible gene that encodes a protein with zinc fingers and that is believed to be involved in transcriptional regulation. Expression of this gene was investigated in murine B lymphocytes stimulated through their receptor for antigen (surface immunoglobulin [sIg]) with antireceptor antibodies (anti-sIg). Rapid (by 15 min) up-regulation of Egr-1 mRNA expression was observed after sIg cross-linking at a dose of anti-sIg sufficient to drive the majority of cells into cell cycle. Interestingly, signaling through sIg on the murine B-lymphoma cell line WEHI-231 did not up-regulate Egr-1 expression even though similar signaling pathways, including up-regulation of c-fos expression, are associated with this receptor in these cells. Importantly, cell growth and proliferation of WEHI-231 cells were inhibited by anti-sIg stimulation, which suggested a relationship between Egr-1 expression and differential processing of receptor immunoglobulin signals with respect to cellular growth responses. This notion was further supported by the finding that murine B lymphomas whose proliferation was not inhibited by anti-sIg showed receptor immunoglobulin-coupled Egr-1 expression. In further support of this association are results showing that under conditions in which Egr-1 expression was induced in WEHI-231 cells in response to stimulation by anti-sIg, a concomitant change was observed in the growth response of these cells. These results, then, indicate a potential role for Egr-1 expression in the translation of receptor-generated signals into cellular activation or induced unresponsiveness.
Seyfert
V L
VL
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Sukhatme
V P
VP
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D008667:Metalloproteins / Q000235:genetics*; D051379:Mice; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; D008667:Metalloproteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell