Regular article
A defect in the protein kinase C system in T cells from patients with systemic lupus erythematosus

https://doi.org/10.1016/0090-1229(91)90065-IGet rights and content

Abstract

To determine whether there is an intrinsic defect in T cells from patients with systemic lupus erythematosus (SLE), we studied signal transduction systems, assaying the total protein kinase C (PKC) levels and the phorbol myristate acetate (PMA)-induced activation of PKC in PHA-treated T cells. T cells from SLE patients showed a decrease in proliferation in response to PMA, but not to PHA, thereby suggesting the existence of an intrinsic abnormality in the PKC-mediated activation pathway. Total PKC activity in the T cells from SLE patients was significantly decreased. Although stimulation with PMA induced a translocation of PKC from the cytosol to the particulate fraction, translocated PKC activity after 2 nM PMA treatment was decreased in the SLE T cells. Furthermore, PMA-induced phosphorylation of 80-kDa substrates was also decreased in SLE T cells. These results suggest that there is a reduced PKC activity and an impaired PKC activation in response to PMA in the SLE T cells, a finding which may explain, if partially, the defect in T cell activation in patients with SLE.

References (36)

  • N. Isakov et al.

    Human T lymphocyte activation by tumor promoters: Role of protein kinase C

    J. Immunol.

    (1987)
  • B. Manger et al.

    The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex: Effects of stimulation with soluble or immobilized CD3 antibodies

    J. Immunol.

    (1987)
  • A.E. Nel et al.

    Reaction of T lymphocytes with anti-T3 induces translocation of C-kinase activity to the membrane and specific substrate phosphorylation

    J. Immunol.

    (1987)
  • M.V. Taylor et al.

    Mitogens increase phosphorylation of phosphoinositides in thymocytes

    Nature

    (1984)
  • J.B. Imboden et al.

    Transmembrane signaling by the T cell antigen receptor: Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores

    J. Exp. Med.

    (1985)
  • E.R. Nisbet-Brown et al.

    Antigen-specific and -nonspecific mitogenic signals in the activation of human T cell clones

    J. Immunol.

    (1987)
  • Y. Nishizuka

    The role of protein kinase C in cell surface signal transduction and tumor promotion

    Nature

    (1984)
  • M.J. Berridge et al.

    Inositol trisphosphate, a novel second messenger in cellular signal transduction

    Nature

    (1984)
  • Cited by (0)

    View full text