A defect in the protein kinase C system in T cells from patients with systemic lupus erythematosus.
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.
Tada
Y
Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nagasawa
K
K
Yamauchi
Y
Y
Tsukamoto
H
H
Niho
Y
Y
D001693:Biological Transport, Active; D002455:Cell Division; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology*; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010835:Phytohemagglutinins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate