The GTPase Rac-1 has the potential for pleiotropic functions due to its abi
lity to interact with multiple effecters, Here, activation of Rac-1 is show
n to potently regulate pre-T cell differentiation and proliferation at the
point of T cell antigen receptor (TCR) beta selection. An activated Rac-1 e
ffector domain mutant that restricts signaling to particular actions on act
in dynamics can drive prei cell differentiation. Rac-1 activation cannot fu
lly 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 a
s critical regulators of TCR beta selection.