Activation of phospholipase D following perturbation of the human T lymphocyte antigen receptor/CD3 complex is dependent upon protein kinase C.
Perturbation of the T lymphocyte antigen receptor/CD3 complex or phorbol ester stimulation leads to activation of phospholipase D in the Jurkat T lymphocyte cell line. These observations suggested that phospholipase D activation might result from activation of protein kinase C. In other systems, phospholipase D activity has been shown to be under G-protein or protein kinase C control. Studies detailed here demonstrate that commonly used inhibitors of protein kinase C had unrelated, diverse effects on phospholipase D activity in T lymphocytes. However, protein kinase C down-regulation resulting from prolonged cellular exposure to phorbol esters led to abrogation of anti-CD3-stimulated phospholipase D activation. The results presented underline the complexity of studies employing inhibitors of protein kinase C, suggest interesting approaches to isolation of phospholipase D dependent signalling pathways, confirm that T cell antigen receptor-linked activation of phospholipase D is dependent upon protein kinase C activity and suggest that distant events of T lymphocyte activation are dependent upon the establishment of a positive feedback loop involving protein kinase C and phospholipase D which would result in the prolonged activation of protein kinase C required for certain lymphokine production.
Stewart
S J
SJ
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Cunningham
G R
GR
House
F S
FS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005246:Feedback; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D016853:Muromonab-CD3 / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D007546:Isoquinolines; D016853:Muromonab-CD3; D009363:Neoplasm Proteins; D010879:Piperazines; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate