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Lipid raft targeting of hematopoietic protein tyrosine phosphatase by protein kinase C theta-mediated phosphorylation.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2006 Mar; Vol. 26 (5), pp. 1806-16. - Publication Year :
- 2006
-
Abstract
- Protein kinase C theta (PKC theta) is unique among PKC isozymes in its translocation to the center of the immune synapse in T cells and its unique downstream signaling. Here we show that the hematopoietic protein tyrosine phosphatase (HePTP) also accumulates in the immune synapse in a PKC theta-dependent manner upon antigen recognition by T cells and is phosphorylated by PKC theta at Ser-225, which is required for lipid raft translocation. Immune synapse translocation was completely absent in antigen-specific T cells from PKC theta-/- mice. In intact T cells, HePTP-S225A enhanced T-cell receptor (TCR)-induced NFAT/AP-1 transactivation, while the acidic substitution mutant was as efficient as wild-type HePTP. We conclude that HePTP is phosphorylated in the immune synapse by PKC theta and thereby targeted to lipid rafts to temper TCR signaling. This represents a novel mechanism for the active immune synapse recruitment and activation of a phosphatase in TCR signaling.
- Subjects :
- Animals
Catalytic Domain
Extracellular Signal-Regulated MAP Kinases metabolism
Humans
Intracellular Signaling Peptides and Proteins genetics
Isoenzymes genetics
Jurkat Cells immunology
Jurkat Cells metabolism
Mice
Phosphorylation
Protein Kinase C genetics
Protein Kinase C-theta
Protein Tyrosine Phosphatases genetics
Protein Tyrosine Phosphatases, Non-Receptor
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell metabolism
Serine metabolism
Signal Transduction
T-Lymphocytes immunology
Transgenes
Intracellular Signaling Peptides and Proteins metabolism
Isoenzymes metabolism
Membrane Microdomains metabolism
Protein Kinase C metabolism
Protein Tyrosine Phosphatases metabolism
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16479000
- Full Text :
- https://doi.org/10.1128/MCB.26.5.1806-1816.2006