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Essential function for the GTPase TC21 in homeostatic antigen receptor signaling

AuthorsDelgado, Pilar ; Cubelos, Beatriz ; Calleja, Enrique; Martínez-Martín, Nuria ; Ciprés, Ángel; Mérida, Isabel ; Bustelo, Xosé R. ; Alarcón, Balbino
Issue Date28-Jun-2009
PublisherNature Publishing Group
CitationNature Immunology (2009), doi: 10.1038/ni.1749 (In press)
AbstractT 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.
Description10 pages, 7 figures.-- Article in press.
Supporting information available at: http://www.nature.com/ni/journal/vaop/ncurrent/suppinfo/ni.1749_S1.html
Publisher version (URL)http://dx.doi.org/10.1038/ni.1749
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