Abstract
Activation of mitogen-activated protein kinase (MAPK) pathways leads to cellular differentiation and/or proliferation in a wide variety of cell types, including developing thymocytes. The basic helix-loop-helix (bHLH) proteins E12 and E47 and an inhibitor HLH protein, Id3, play key roles in thymocyte differentiation. We show here that E2A DNA binding is lowered in primary immature thymocytes consequent to T cell receptor (TCR)-mediated ligation. Whereas expression of E2A mRNA and protein are unaltered, Id3 transcripts are rapidly induced upon signaling from the TCR. Activation of Id3 transcription is regulated in a dose-dependent manner by the extracellular signal-regulated kinase (ERK) MAPK module. These observations directly connect the ERK MAPK cascade and HLH proteins in a linear pathway.
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Acknowledgements
We thank M. Karin for the MKK1-ED cDNA; B. Sefton for the LckF505 cDNA and R. Rivera for the Id3 northern probe. Supported, in part, by the California Division-American Cancer Society, Fellowship number 1-3-00 (to G. B.) and the National Institutes of Health (to C. M., J. A. and S. H.).
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Bain, G., Cravatt, C., Loomans, C. et al. Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nat Immunol 2, 165–171 (2001). https://doi.org/10.1038/84273
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DOI: https://doi.org/10.1038/84273
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