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

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.