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Control of pre-T cell proliferation and differentiation by the GTPase Rac-I
M Gomez1, V Tybulewicz, D A Cantrell
1Imperial Cancer Research Fund, Lymphocyte Activation Laboratory, 44 Lincolns Inn Fields, London WC2A3PX, UK.
Abstract:
The GTPase Rac-I has the potential for pleiotropic functions due to its ability to interact with multiple effectors. Here, activation of Rac-I is shown to potently regulate pre-T cell differentiation and proliferation at the point of T cell antigen receptor (TCR) beta selection. An activated Rac-I effector domain mutant that restricts signaling to particular actions on actin dynamics can drive pre-T cell differentiation. Rac-I 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-I responses that mediate Vav-1 action as critical regulators of TCR beta selection.