Essential function for the GTPase TC21 in homeostatic antigen receptor signaling.
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.
Delgado
Pilar
P
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Cubelos
Beatriz
B
Calleja
Enrique
E
Martínez-Martín
Nuria
N
Ciprés
Angel
A
Mérida
Isabel
I
Bellas
Carmen
C
Bustelo
Xosé R
XR
Alarcón
Balbino
B
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D006706:Homeostasis; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D019869:Phosphatidylinositol 3-Kinases; C087360:RRAS2 protein, human; C490200:Rras2 protein, mouse; D020559:Monomeric GTP-Binding Proteins