Control of pre-T cell proliferation and differentiation by the GTPase Rac-I.
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.
Gomez
M
M
Imperial Cancer Research Fund, Lymphocyte Activation Laboratory, 44 Lincolns Inn Fields, London WC2A3PX, UK.
Tybulewicz
V
V
Cantrell
D A
DA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D006801:Humans; D051379:Mice; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D020830:rac1 GTP-Binding Protein