Deficiency of small GTPase Rac2 affects T cell activation

Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to med iate both transcriptional activation and cell morphological changes. We hav e examined the effect of Rac2 deficiency during T cell activation. In Rac2( -/-) T cells, proliferation was reduced upon stimulation with either plate- bound anti-CD3 or T cell receptor-specific antigen. This defect is accompan ied with decreased activation of mitogen activated protein kinase extracell ular signal-regulated kinase (EP-K) 1/2 and p38, and reduced Ca2+ mobilizat ion. TCR stimulation-induced actin polymerization is also reduced. In addit ion, anti-CD3 cross-linking-induced T cell capping is reduced compared with wild-ty-pe T cells. These results indicate that Rac2 is important in media ting both transcriptional and cytoskeletal changes during T cell activation . The phenotypic similarity of Rac2(-/-) to Vav(-/-) cells implicates Rac2 as a downstream mediator of Vav signaling.