Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD3 Complex / immunology
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Calcium Signaling
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Cell Cycle Proteins*
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Enzyme Activation
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Lymphocyte Activation / immunology*
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Mice
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Mice, Mutant Strains
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Mice, Transgenic
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-vav
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RAC2 GTP-Binding Protein
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes / immunology*
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p38 Mitogen-Activated Protein Kinases
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rac GTP-Binding Proteins / deficiency*
Substances
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CD3 Complex
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Cell Cycle Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell
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Vav1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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rac GTP-Binding Proteins