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Disruption of T cell signaling networks and development by Grb2 haploid insufficiency

Gong, Qian and Cheng, Alec M. and Akk, Antonina M. and Alberola-Ila, José and Gong, Guoqing and Pawson, Tony and Chan, Andrew C. (2001) Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Nature Immunology, 2 (1). pp. 29-36. ISSN 1529-2908. doi:10.1038/83134.

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The developmental processes of positive and negative selection in the thymus shape the T cell antigen receptor (TCR) repertoire and require the integration of multiple signaling networks. These networks involve the efficient assembly of macromolecular complexes and are mediated by multimodular adaptor proteins that permit the functional integration of distinct signaling molecules. We show here that decreased expression of the adaptor protein Grb2 in Grb2 +/- mice weakens TCR-induced c-Jun N-terminal kinase (JNK) and p38, but not extracellular signal−regulated kinase (ERK), activation. In turn, this selective effect decreases the ability of thymocytes to undergo negative, but not positive, selection. We also show that there are differences in the signaling thresholds of the three mitogen-activated protein kinase (MAPK) families. These differences may provide a mechanism by which quantitative differences in signal strength can alter the balance of downstream signaling pathways to induce the qualitatively distinct biological outcomes of proliferation, differentiation or apoptosis.

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Additional Information:© 2001 Nature Publishing Group. Received 25 October 2000; accepted 7 November 2000. We thank K. Blumer, H. Piwnica-Worms, T. Chatila, A. Shaw and P. Allen for critical reading of the manuscript and A. Weiss and R. Germain for critical discussion of the data. Supported, in part, by the National Institutes of Health (grant number AI47330), the Medical Research Council of Canada (to T. P.) and a Terry Fox Program Project Grant from the National Cancer Institute of Canada (to T. P.). T. P. is a Distinguished Scientist of the Medical Research Council.
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Medical Research Council of CanadaUNSPECIFIED
National Cancer Institute of CanadaUNSPECIFIED
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Record Number:CaltechAUTHORS:20150406-155123000
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56403
Deposited By: Tony Diaz
Deposited On:06 Apr 2015 23:04
Last Modified:10 Nov 2021 20:58

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