Deficiency of small GTPase Rac2 affects T cell activation

被引:95
作者
Yu, H
Leitenberg, D
Li, BY
Flavell, RA
机构
[1] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
T cell activation; Rac2; VAV; MAPK; cytoskeleton;
D O I
10.1084/jem.194.7.915
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (EP-K) 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-ty-pe 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.
引用
收藏
页码:915 / 925
页数:11
相关论文
共 62 条
[1]   ACTIVATION OF THE NADPH OXIDASE INVOLVES THE SMALL GTP-BINDING PROTEIN P21RAC1 [J].
ABO, A ;
PICK, E ;
HALL, A ;
TOTTY, N ;
TEAHAN, CG ;
SEGAL, AW .
NATURE, 1991, 353 (6345) :668-670
[2]   T cell activation and the cytoskeleton [J].
Acuto, O ;
Cantrell, D .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :165-+
[3]  
Allen WE, 1997, J CELL SCI, V110, P707
[4]   Rac is involved in early TCR signaling [J].
Arrieumerlou, C ;
Randriamampita, C ;
Bismuth, G ;
Trautmann, A .
JOURNAL OF IMMUNOLOGY, 2000, 165 (06) :3182-3189
[5]   Activation of phospholipase C-γ by phosphatidylinositol 3,4,5-trisphosphate [J].
Bae, YS ;
Cantley, LG ;
Chen, CS ;
Kim, SR ;
Kwon, KS ;
Rhee, SG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) :4465-4469
[6]   PAK to the future [J].
Bagrodia, S ;
Cerione, RA .
TRENDS IN CELL BIOLOGY, 1999, 9 (09) :350-355
[7]   THE SMALL GTP-BINDING PROTEIN-RHO REGULATES A PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE IN MAMMALIAN-CELLS [J].
CHONG, LD ;
TRAYNORKAPLAN, A ;
BOKOCH, GM ;
SCHWARTZ, MA .
CELL, 1994, 79 (03) :507-513
[8]   Selective induction of apoptosis in mature T lymphocytes by variant T cell receptor ligands [J].
Combadiere, B ;
Sousa, CRE ;
Germain, RN ;
Lenardo, MJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (03) :349-355
[9]   THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, M ;
YU, JC ;
TERAMOTO, H ;
CRESPO, P ;
XU, NG ;
MIKI, T ;
GUTKIND, JS .
CELL, 1995, 81 (07) :1137-1146
[10]   The Rho-family GTP exchange factor Vav is a critical transducer of T cell receptor signals to the calcium, ERK, and NF-κB pathways [J].
Costello, PS ;
Walters, AE ;
Mee, PJ ;
Turner, M ;
Reynolds, LF ;
Prisco, A ;
Sarner, N ;
Zamoyska, R ;
Tybulewicz, VLJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3035-3040