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PMID: 16479000 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Molecular and cellular biology ·Vol. 26 ·No. 5 ·2006-03-00 ·Pages 1806-16

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

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.

MeSH Terms
Animals Catalytic Domain Extracellular Signal-Regulated MAP Kinases/metabolism Humans Intracellular Signaling Peptides and Proteins/genetics,metabolism Isoenzymes/genetics,metabolism Jurkat Cells/immunology,metabolism Membrane Microdomains/metabolism Mice Phosphorylation Protein Kinase C/genetics,metabolism Protein Kinase C-theta Protein Tyrosine Phosphatases/genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor Receptors, Antigen, T-Cell/genetics,metabolism Serine/metabolism Signal Transduction T-Lymphocytes/immunology,metabolism Transgenes
Chemicals
Intracellular Signaling Peptides and Proteins Isoenzymes Receptors, Antigen, T-Cell Serine PRKCQ protein, human Protein Kinase C Protein Kinase C-theta Extracellular Signal-Regulated MAP Kinases PTPN7 protein, human Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Nika Konstantina
Program of Inflammation, Infectious and Inflammatory Disease Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
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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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.5.1806-1816.2006
Published
2006-03-00
Pages
1806-16
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1430257
Subset
IM
Grants
NIAID NIH HHS · AI53585 · United States
NCI NIH HHS · R01 CA096949 · United States
NIAID NIH HHS · R01 AI035603 · United States
NCI NIH HHS · CA96949 · United States
NIAID NIH HHS · AI35603 · United States
NIAID NIH HHS · AI55741 · United States
NIAID NIH HHS · AI48032 · United States
NIAID NIH HHS · R01 AI053585 · United States
NIAID NIH HHS · R01 AI055741 · United States
NIAID NIH HHS · R01 AI048032 · United States
External Links
PubMed source DOI: 10.1128/MCB.26.5.1806-1816.2006 PMC Full Text View journal details
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