CD45-Csk Phosphatase-Kinase Titration Uncouples Basal and Inducible T Cell Receptor Signaling during Thymic development
Date
2010
Authors
Zikherman, Julie
Jenne, Craig N
Watson, Susan R
Doan, Kristin
Raschke, William
Goodnow, Christopher
Weiss, Arthur
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Publisher
Cell Press
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.
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Keywords
Keywords: CD45 antigen; phosphatase; phosphotransferase; protein Csk; T lymphocyte receptor; unclassified drug; animal cell; animal experiment; antigen expression; article; controlled study; down regulation; enzyme phosphorylation; mouse; nonhuman; organogenesis; p Cellimmuno; Molimmuno
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Source
Immunity
Type
Journal article
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2037-12-31
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