c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain.
Interleukin 2 (IL-2) plays a critical role in the growth and differentiation of lymphoid cells. The IL-2 signal is delivered intracellularly by the IL-2 receptor beta chain (IL-2R beta); however, the mechanism by which the signal reaches the nucleus remains unclear. In this study, we demonstrate the rapid activation of c-fos protooncogene transcription by IL-2 and provide evidence that the serum-responsive element (SRE) within the c-fos promoter is responsible for the activation in a murine pro-B-cell line, BAF-B03, expressing the human IL-2R beta cDNA. Interestingly, the same SRE is also responsible for c-fos gene activation by interleukin 3 or erythropoietin. Further, we show that the activation of c-fos by IL-2 requires defined cytoplasmic regions of IL-2R beta--i.e., the "serine-rich" region, which is known to be essential for growth-signal transduction in BAF-B03 cells, and the "acidic region," which is located more distal to the cell membrane. These results indicate the functional importance of the two distinct regions within the IL-2R beta cytoplasmic domain in IL-2-induced c-fos gene activation and point to a potential role of the acidic region in IL-2 signal transduction that could not be adequately assessed in a previous study.
Hatakeyama
M
M
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kawahara
A
A
Mori
H
H
Shibuya
H
H
Taniguchi
T
T
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D010957:Plasmids; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection
D007376:Interleukin-2; D007377:Interleukin-3; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D015500:Chloramphenicol O-Acetyltransferase