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Original Article

^a Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
^b Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
Section of Immunobiology, Yale University School of Medicine, 310 Cedar St., FMB 412, New Haven, CT 06520.203-737-2958203-737-2216

richard.flavell{at}yale.edu

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 Ca²+ 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.

Key Words: T cell activation • Rac2 • VAV • MAPK • cytoskeleton

B. Li's present address is Pfizer, Inc., East Point Rd., Groton, CT 06340.

Abbreviations used in this paper: ERK, extracellular signal–regulated kinase; JNK, c-Jun NH₂-terminal kinase; KO, knockout; MAPK, mitogen-activated protein kinase; SMAC, supramolecular activation cluster; GEF, guanine nucleotide exchange factor.

© 2001 The Rockefeller University Press

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