Division of Rheumatology, University of California San Francisco, San Francisco, CA 94143, USA.
Immunity. 2010 Mar 26;32(3):342-54. doi: 10.1016/j.immuni.2010.03.006.
The kinase-phosphatase pair Csk and CD45 reciprocally regulate phosphorylation of the inhibitory tyrosine of the Src family kinases Lck and Fyn. T cell receptor (TCR) signaling and thymic development require CD45 expression but proceed constitutively in the absence of Csk. Here, we show that relative titration of CD45 and Csk expression reveals distinct regulation of basal and inducible TCR signaling during thymic development. Low CD45 expression is sufficient to rescue inducible TCR signaling and positive selection, whereas high expression is required to reconstitute basal TCR signaling and beta selection. CD45 has a dual positive and negative regulatory role during inducible but not basal TCR signaling. By contrast, Csk titration regulates basal but not inducible signaling. High physiologic expression of CD45 is thus required for two reasons-to downmodulate inducible TCR signaling during positive selection and to counteract Csk during basal TCR signaling.
激酶-磷酸酶对 Csk 和 CD45 相互调节 Src 家族激酶 Lck 和 Fyn 的抑制性酪氨酸的磷酸化。T 细胞受体 (TCR) 信号和胸腺发育需要 CD45 的表达，但在没有 Csk 的情况下持续进行。在这里，我们表明，CD45 和 Csk 表达的相对滴定揭示了胸腺发育过程中基础和诱导性 TCR 信号的不同调节。低表达 CD45 足以挽救诱导性 TCR 信号和阳性选择，而高表达则需要重建基础 TCR 信号和β选择。CD45 在诱导性但不是基础 TCR 信号中具有双重正调节和负调节作用。相比之下，Csk 滴定调节基础但不调节诱导性信号。因此，高生理表达的 CD45 需要两个原因——在阳性选择期间下调诱导性 TCR 信号，以及在基础 TCR 信号期间对抗 Csk。
