@article{26e617d054aa11dd8d9f000ea68e967b,
title = "The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation.",
abstract = "Cell surface expression of CD45, a receptor-like protein tyrosine phosphatase (PTPase), is required for T cell antigen receptor (TCR)-mediated signal transduction. Like the majority of transmembrane PTPases, CD45 contains two cytoplasmic phosphatase domains, whose relative in vivo function is not known. Site-directed mutagenesis of the individual catalytic residues of the two CD45 phosphatase domains indicates that the catalytic activity of the membrane-proximal domain is both necessary and sufficient for restoration of TCR signal transduction in a CD45-deficient cell. The putative catalytic activity of the distal phosphatase domain is not required for proximal TCR-mediated signaling events. Moreover, in the context of a chimeric PTPase receptor, the putative catalytic activity of the distal phosphatase domain is not required for ligand-induced negative regulation of PTPase function. We also demonstrate that the phosphorylation of the C-terminal tyrosine of Lck, a site of negative regulation, is reduced only when CD45 mutants with demonstrable in vitro phosphatase activity are introduced into the CD45-deficient cells. These results demonstrate that the phosphatase activity of CD45 is critical for TCR signaling, and for regulating the levels of C-terminal phosphorylated Lck molecules.",
author = "Desai, {D M} and J Sap and O Silvennoinen and J Schlessinger and A Weiss",
note = "Keywords: Amino Acid Sequence; Antigens, CD45; Catalysis; DNA Mutational Analysis; Ligands; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Molecular Sequence Data; Phosphorylation; Point Mutation; Protein Processing, Post-Translational; Protein Tyrosine Phosphatases; Protein-Tyrosine Kinases; Receptor, Epidermal Growth Factor; Receptors, Antigen, T-Cell; Recombinant Fusion Proteins; Signal Transduction; Structure-Activity Relationship; Tyrosine",
year = "1994",
language = "English",
volume = "13",
pages = "4002--10",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "17",
}