The antigen receptors on mature and immature T lymphocytes are coupled to phosphatidylcholine-specific phospholipase D activation.
Phosphatidylcholine-phospholipase D has been proposed to play a key role in the transduction of the proliferative responses of a wide range of mitogens and growth factors. We now report that the antigen receptors on T lymphocytes derived from human tonsillar or murine splenic preparations are coupled to phosphatidylcholine (PtdCho)-phospholipase D (PLD) activation following stimulation of these T cells with anti-CD3 antibodies. However, since we also demonstrate that the antigen receptors on murine thymocytes are coupled to PtdCho-PLD activation, we propose that it is unlikely that this PLD pathway plays a central role in the transduction of T-cell proliferative responses, but rather, may be involved in either driving cells into cycle or maintaining cell cycle progression, processes required both for proliferation and activation-induced cell death. Whilst the molecular mechanisms underlying T-cell receptor (TCR)-coupling to PtdCho-PLD activation in these cells have not been fully defined, kinetics studies and experiments using pharmacological inhibitors of protein tyrosine phosphatases (PTPases) and reconstituting CD3-coupled PtdCho-PLD activity in streptolysin-O permeabilized cells, suggest that the TCR/CD3 complex, under optimal conditions of activation, may be predominantly coupled to PtdCho-PLD activation downstream of tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma), phosphatidylinositol (PtdIns)P2 hydrolysis, calcium mobilization and protein kinase C (PKC) activation.
Reid
P A
PA
Division of Biochemistry and Molecular Biology, University of Glasgow, UK.
Gardner
S D
SD
Williams
D M
DM
Harnett
M M
MM
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D010713:Phosphatidylcholines; D011948:Receptors, Antigen, T-Cell; D010739:Phospholipase D