CD45-Csk Phosphatase-Kinase Titration Uncouples Basal and Inducible T Cell Receptor Signaling during Thymic Development

Julie Zikherman, Craig Jenne, Susan Watson, Kristin Doan, William Raschke, Christopher C. Goodnow, Arthur Weiss*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    78 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)342-354
    Number of pages13
    JournalImmunity
    Volume32
    Issue number3
    DOIs
    Publication statusPublished - Mar 2010

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