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J. Biol. Chem., Vol. 278, Issue 16, 14059-14065, April 18, 2003
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From the CD45 is the major protein tyrosine phosphatase
receptor on T cell surfaces that functions as both a positive and a
negative regulator of T cell receptor (TCR) signaling. Although CD45 is required for the activation of TCR-associated Src
family kinases, it also dephosphorylates phosphoproteins
involved in the TCR-signaling cascade. This study links CD45 to the
inhibitory activity of placental protein 14 (PP14), a major soluble
protein of pregnancy that is now known to be a direct modulator of T
cells and to function by desensitizing TCR signaling. PP14 and CD45
co-capped with each other, pointing to a physical linkage between the
two. Interestingly, however, the binding of PP14 to T cell
surfaces was not restricted to CD45 alone, with evidence showing that
PP14 binds to other surface molecules in a
carbohydrate-dependent fashion. Notwithstanding the broader
molecular binding potential of PP14, its interaction with CD45 appeared
to have special functional significance. Using transfected derivatives
of the HPB.ALL mutant T cell line that differ in CD45 expression, we
established that the inhibitory effects of PP14 are dependent upon the
expression of intact CD45 on T cell surfaces. Based upon these
findings, we propose a new immunoregulatory model for PP14, wherein one
of its surface molecular targets, CD45, mediates its T cell inhibitory
activity, accounting for the intriguing capacity of PP14 to elevate TCR
activation thresholds and thereby down-regulate T cell activation.
Negative Regulation of T Cell Activation by Placental
Protein 14 Is Mediated by the Tyrosine Phosphatase Receptor
CD45*
§,,
Goldyne Savad Institute of Gene Therapy,
Hadassah University Hospital, Jerusalem 91120, Israel, the
¶ Department of Pathology, Case Western Reserve University,
Cleveland, Ohio 44106, and the Department of Pathology and
Laboratory Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 19104
*
This study was supported by National Institutes of Health
Grant R01 AI-38960 and the Greensboro Community Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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