Article abstract
Nature Immunology 10, 880 - 888 (2009)
Published online: 28 June 2009 | doi:10.1038/ni.1749
Essential function for the GTPase TC21 in homeostatic antigen receptor signaling
Pilar Delgado1, Beatriz Cubelos1, Enrique Calleja1, Nuria Martínez-Martín1, Angel Ciprés2, Isabel Mérida2, Carmen Bellas3, Xosé R Bustelo4 & Balbino Alarcón1
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 p110
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.
- Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
- Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
- Laboratory of Molecular Pathology, Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
- Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Cientificas–University of Salamanca, Salamanca, Spain.
Correspondence to: Balbino Alarcón1 e-mail: balarcon@cbm.uam.es
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