Lipid raft targeting of hematopoietic protein tyrosine phosphatase by protein kinase C theta-mediated phosphorylation |
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Authors: | Nika Konstantina Charvet Céline Williams Scott Tautz Lutz Bruckner Shane Rahmouni Souad Bottini Nunzio Schoenberger Stephen P Baier Gottfried Altman Amnon Mustelin Tomas |
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Institution: | Program of Inflammation, Infectious and Inflammatory Disease Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. |
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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. |
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