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Control of pre-T cell proliferation and differentiation by the GTPase Rac-1

Nature Immunology volume 1, pages 348–352 (2000)Cite this article

Abstract

The GTPase Rac-1 has the potential for pleiotropic functions due to its ability to interact with multiple effectors. Here, activation of Rac-1 is shown to potently regulate pre-T cell differentiation and proliferation at the point of T cell antigen receptor (TCR) β selection. An activated Rac-1 effector domain mutant that restricts signaling to particular actions on actin dynamics can drive pre-T cell differentiation. Rac-1 activation cannot fully substitute for the pre-TCR complex but can fully correct defects in pre-T cell development in mice lacking the adapter molecule Vav-1. The present study identifies the subset of Rac-1 responses that mediate Vav-1 action as critical regulators of TCRβ selection.

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Figure 1: Generation of L61Rac-1 transgenic mice.
Figure 2: Pre-TCR–mediated responses are enhanced in L61Rac-1 transgenic mice.
Figure 3: Activated Rac-1 restores CD4+CD8+ DP differentiation in RAG-1−/− mice.
Figure 4: Pre-TCR mediated responses are enhanced in L61Y40CRac-1 transgenic mice.
Figure 5: Activated Rac-1 restores pre-T cell differentiation and thymocyte cellularity in Vav-1−/− mice.

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Acknowledgements

We thank I. Rosewell for injection of transgenic constructs, and T. Crafton, S. Hoskins, J. Bee and G. Hutchinson for animal care. Supported by the Imperial Cancer Research Fund, European Community Training and Mobility of Researchers Program (to M. G.; ERBFMICT 972245) and the Medical Research Council (to V. T.).

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Lymphocyte Activation Laboratory, 44 Lincolns Inn Fields, London, WC2A3PX, UK

    Manuel Gomez & Doreen A. Cantrell

  2. National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Victor Tybulewicz

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Correspondence to Doreen A. Cantrell.

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Gomez, M., Tybulewicz, V. & Cantrell, D. Control of pre-T cell proliferation and differentiation by the GTPase Rac-1. Nat Immunol 1, 348–352 (2000). https://doi.org/10.1038/79808

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