The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 1 October 2001. doi:10.1084/jem.194.7.903
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 258K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corre, I.
Right arrow Articles by Cantrell, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corre, I.
Right arrow Articles by Cantrell, D. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/10/903/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 7, October 1, 2001 903-914

Original Article

Analysis of Thymocyte Development Reveals That the Gtpase Rhoa Is a Positive Regulator of T Cell Receptor Responses in Vivo

Isabelle Correa, Manuel Gomeza, Susina Vielkinda, and Doreen A. Cantrella

a Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, 44 Lincoln Inn Fields, London, WC2A 3PX, UK.44-020-7269-347944-020-7269-3307

d.cantrell{at}icrf.icnet.uk

Loss of function of the guanine nucleotide binding protein RhoA blocks pre-T cell differentiation and survival indicating that this GTPase is a critical signaling molecule during early thymocyte development. Previous work has shown that the Rho family GTPase Rac-1 can initiate changes in actin dynamics necessary and sufficient for pre-T cell development. The present data now show that Rac-1 actions in pre-T cells require Rho function but that RhoA cannot substitute for Rac-1 and induce the actin cytoskeletal changes necessary for pre-T cell development. Activation of Rho is thus not sufficient to induce pre-T cell differentiation or survival in the absence of the pre-T cell receptor (TCR). The failure of RhoA activation to impact on pre-TCR–mediated signaling was in marked contrast to its actions on T cell responses mediated by the mature TCR {alpha}/β complex. Cells expressing active RhoA were thus hyperresponsive in the context of TCR-induced proliferation in vitro and in vivo showed augmented positive selection of thymocytes expressing defined TCR complexes. This reveals that RhoA function is not only important for pre-T cells but also plays a role in determining the fate of mature T cells.

Key Words: Rac-1 • Vav-1 • RhoA • antigen receptor • pre-T cell receptor

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; DN, double negative; DP, double positive; GEF, guanine nucleotide exchange factor; LCR, locus control region; NLC, normal littermate control; PdBu, phorbol-12,13 dibutyrate; Rag, recombinase activating gene; SP, single positive.

© 2001 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS