Deficiency of small GTPase Rac2 affects T cell activation.
Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to mediate both transcriptional activation and cell morphological changes. We have 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 accompanied with decreased activation of mitogen activated protein kinase extracellular signal-regulated kinase (ERK)1/2 and p38, and reduced Ca(2)+ mobilization. TCR stimulation-induced actin polymerization is also reduced. In addition, anti-CD3 cross-linking-induced T cell capping is reduced compared with wild-type T cells. These results indicate that Rac2 is important in mediating 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.
Yu
H
H
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Leitenberg
D
D
Li
B
B
Flavell
R A
RA
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D020013:Calcium Signaling; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins / Q000172:deficiency*; D000097766:RAC2 GTP-Binding Protein
D017252:CD3 Complex; D018797:Cell Cycle Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D048051:p38 Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C496619:Vav1 protein, mouse