GTP酶TC21在稳态抗原受体信号传导中的重要功能。
Essential function for the GTPase TC21 in homeostatic antigen receptor signaling.
作者信息
Delgado Pilar, Cubelos Beatriz, Calleja Enrique, Martínez-Martín Nuria, Ciprés Angel, Mérida Isabel, Bellas Carmen, Bustelo Xosé R, Alarcón Balbino
机构信息
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Spain.
出版信息
Nat Immunol. 2009 Aug;10(8):880-8. doi: 10.1038/ni.1749. Epub 2009 Jun 28.
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.
T细胞抗原受体（TCR）和B细胞抗原受体（BCR）传递成熟细胞库生存和维持所必需的低水平信号。我们在此表明，由Rras2编码的小GTP酶TC21与这两种受体持续相互作用。在T细胞中表达显性负性TC21突变体导致细胞活力迅速下降，并且Rras2基因敲除小鼠出现淋巴细胞减少，这可能是由于稳态增殖减少以及T细胞和B细胞存活受损所致。相反，TC21在几种人类淋巴恶性肿瘤中过表达。最后，磷脂酰肌醇-3-羟基激酶（PI(3)K）的p110δ催化亚基以TC21依赖的方式被募集到TCR和BCR。因此，我们提出TC21直接将抗原受体与PI(3)K介导的生存途径联系起来。
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