Two distinct pathways exist for down-regulation of the TCR
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Two distinct pathways exist for down-regulation of the TCR. / Lauritsen, J P; Christensen, M D; Dietrich, J; Kastrup, J; Odum, N; Geisler, C.
In: Journal of Immunology, Vol. 161, No. 1, 1998, p. 260-7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Two distinct pathways exist for down-regulation of the TCR
AU - Lauritsen, J P
AU - Christensen, M D
AU - Dietrich, J
AU - Kastrup, J
AU - Odum, N
AU - Geisler, C
N1 - Keywords: Amino Acid Sequence; Down-Regulation; Humans; Jurkat Cells; Ligands; Molecular Sequence Data; Phosphoprotein Phosphatases; Phosphorylation; Protein Kinase C; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Antigen, T-Cell; T-Lymphocytes; Tyrosine; src-Family Kinases
PY - 1998
Y1 - 1998
N2 - TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. Down-regulation of the TCR is induced by engagement of the TCR by specific ligands and/or by activation of protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down-regulation is mediated by two distinct, independent mechanisms. Ligand-induced TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation is dependent on the CD3gamma L-based internalization motif but independent of p56(lck) and p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR expression levels can be finely regulated via the CD3gamma L-based motif by the balance between PKC and serine/threonine protein phosphatase activities. Such a TCR ligation-independent regulation of TCR expression levels could probably be important in determining the activation threshold of T cells in their encounter with APC.
AB - TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. Down-regulation of the TCR is induced by engagement of the TCR by specific ligands and/or by activation of protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down-regulation is mediated by two distinct, independent mechanisms. Ligand-induced TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation is dependent on the CD3gamma L-based internalization motif but independent of p56(lck) and p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR expression levels can be finely regulated via the CD3gamma L-based motif by the balance between PKC and serine/threonine protein phosphatase activities. Such a TCR ligation-independent regulation of TCR expression levels could probably be important in determining the activation threshold of T cells in their encounter with APC.
M3 - Journal article
C2 - 9647232
VL - 161
SP - 260
EP - 267
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -
ID: 8545462