Essential function for the GTPase TC21 in homeostatic antigen receptor signaling

被引：89

作者：

Delgado, Pilar ^{[1
]}

Cubelos, Beatriz ^{[1
]}

Calleja, Enrique ^{[1
]}

Martinez-Martin, Nuria ^{[1
]}

Cipres, Angel ^{[2
]}

Merida, Isabel ^{[2
]}

Bellas, Carmen ^{[3
]}

Bustelo, Xose R. ^{[4
,5
]}

Alarcon, Balbino ^{[1
]}

机构：

[1] CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain

[2] Univ Autonoma Madrid, CSIC, Ctr Nacl Biotecnol, Madrid, Spain

[3] Hosp Univ Puerta Hierro, Dept Pathol, Lab Mol Pathol, Madrid, Spain

[4] Univ Salamanca, CSIC, Ctr Invest Canc, E-37008 Salamanca, Spain

[5] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 08期

关键词：

B-CELL DEVELOPMENT; T-CELLS; PHOSPHATIDYLINOSITOL; 3-KINASE; SURVIVAL SIGNALS; RAS; PROLIFERATION; ACTIVATION; P110-DELTA; PROTEIN; NAIVE;

D O I：

10.1038/ni.1749

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

T cell antigen receptors (TCRs) and B cell antigen receptors (BCRs) transmit low-grade signals necessary for the survival and maintenance of mature cell pools. We show here that TC21, a small GTPase encoded by Rras2, interacted constitutively with both kinds of receptors. Expression of a dominant negative TC21 mutant in T cells produced a rapid decrease in cell viability, and Rras2(-/-) mice were lymphopenic, possibly as a result of diminished homeostatic proliferation and impaired T cell and B cell survival. In contrast, TC21 was overexpressed in several human lymphoid malignancies. Finally, the p110 delta catalytic subunit of phosphatidylinositol-3-OH kinase (PI(3) K) was recruited to the TCR and BCR in a TC21-dependent way. Consequently, we propose TC21 directly links antigen receptors to PI(3) K-mediated survival pathways.

引用

页码：880 / U109

页数：10

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