Lipid raft targeting of hematopoietic protein tyrosine phosphatase by protein kinase C theta-mediated phosphorylation.

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.

journal_name

Mol Cell Biol

authors

Nika K,Charvet C,Williams S,Tautz L,Bruckner S,Rahmouni S,Bottini N,Schoenberger SP,Baier G,Altman A,Mustelin T

doi

10.1128/MCB.26.5.1806-1816.2006

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

1806-16

issue

5

eissn

0270-7306

issn

1098-5549

pii

26/5/1806

journal_volume

26

pub_type

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