Antigen-induced Translocation of PKC-theta to Membrane Rafts Is Required for T Cell Activation

Nat Immunol. 2001 Jun;2(6):556-63. doi: 10.1038/88765.

Abstract

Protein kinase C-theta (PKC-theta) is essential for mature T cell activation; however, the mechanism by which it is recruited to the TCR signaling machinery is unknown. Here we show that T cell stimulation by antibodies or peptide-major histocompatibility complex (MHC) induces translocation of PKC-theta to membrane lipid rafts, which localize to the immunological synapse. Raft translocation was mediated by the PKC-theta regulatory domain and required Lck but not ZAP-70. In addition, PKC-theta was associated with Lck in the rafts. An isolated PKC-straight theta catalytic fragment did not partition into rafts or activate the transcription factor NF-kappa B, although addition of a Lck-derived raft-localization sequence restored these functions. Thus, physiological T cell activation translocates PKC-theta to rafts, which localize to the T cell synapse; this PKC-theta translocation is important for its function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Antigens / metabolism*
  • Biological Transport, Active
  • Humans
  • Isoenzymes / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Membrane Lipids / immunology
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein-Tyrosine Kinases / metabolism
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • Antigens
  • Isoenzymes
  • Membrane Lipids
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta