@article{e0baa8b0b0a311ddb538000ea68e967b,
title = "The phosphorylation state of CD3gamma influences T cell responsiveness and controls T cell receptor cycling",
abstract = "The T cell receptor (TCR) is internalized following activation of protein kinase C (PKC) via a leucine (Leu)-based motif in CD3gamma. Some studies have indicated that the TCR is recycled back to the cell surface following PKC-mediated internalization. The functional state of recycled TCR and the mechanisms involved in the sorting events following PKC-induced internalization are not known. In this study, we demonstrated that following PKC-induced internalization, the TCR is recycled back to the cell surface in a functional state. TCR recycling was dependent on dephosphorylation of CD3gamma, probably mediated by the serine/threonine protein phosphatase-2A, but independent on microtubules or actin polymerization. Furthermore, in contrast to ligand-mediated TCR sorting, recycling of the TCR was independent of the tyrosine phosphatase CD45 and the Src tyrosine kinases p56(Lck) and p59(Fyn). Studies of mutated TCR and chimeric CD4-CD3gamma molecules demonstrated that CD3gamma did not contain a recycling signal in itself. In contrast, the only sorting information in CD3gamma was the Leu-based motif that mediated lysosomal sorting of chimeric CD4-CD3gamma molecules. Finally, we found a correlation between the phosphorylation state of CD3gamma and T cell responsiveness. Based on these observations a physiological role of CD3gamma and TCR cycling is proposed.",
author = "J Dietrich and T B{\"a}ckstr{\"o}m and Lauritsen, {J P} and J Kastrup and Christensen, {M D} and {von B{\"u}low}, F and E Palmer and C Geisler",
note = "Keywords: Amino Acid Sequence; Antigens, CD; Antigens, CD4; Antigens, CD45; Biotinylation; Calcium; Cell Membrane; Cytosol; Humans; Jurkat Cells; Kinetics; Leucine; Lysosomes; Molecular Sequence Data; Phorbol 12,13-Dibutyrate; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 2; Protein-Tyrosine Kinases; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, gamma-delta; Recombinant Fusion Proteins; Sequence Alignment; Sequence Homology, Amino Acid; T-Lymphocytes; Transfection",
year = "1998",
language = "English",
volume = "273",
pages = "24232--8",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "37",
}