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

Mol Cell Biol. 2006 Mar;26(5):1806-16. doi: 10.1128/MCB.26.5.1806-1816.2006.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Catalytic Domain
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Jurkat Cells / immunology
  • Jurkat Cells / metabolism
  • Membrane Microdomains / metabolism*
  • Mice
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Serine / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transgenes


  • 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