Essential function for the GTPase TC21 in homeostatic antigen receptor signaling.
Nat Immunol
; 10(8): 880-8, 2009 Aug.
Article
in En
| MEDLINE
| ID: mdl-19561613
ABSTRACT
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 p110delta 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Receptors, Antigen, B-Cell
/
Receptors, Antigen, T-Cell
/
T-Lymphocytes
/
Monomeric GTP-Binding Proteins
/
Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2009
Type:
Article
Affiliation country:
Spain