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Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade

Bain, Gretchen and Cravatt, Celia B. and Loomans, Cindy and Alberola-Ila, José and Hedrick, Stephen M. and Murre, Cornelis (2001) Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nature Immunology, 2 (2). pp. 165-171. ISSN 1529-2908.

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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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Additional Information:© 2001 Nature Publishing Group. Received 10 October 2000; accepted 14 December 2000. 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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American Cancer Society, California Division1-3-00
Issue or Number:2
Record Number:CaltechAUTHORS:20150407-074526440
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56406
Deposited By: Tony Diaz
Deposited On:07 Apr 2015 21:47
Last Modified:03 Oct 2019 08:13

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