Activation of phospholipase C-gamma 1 through transfected platelet-derived growth factor receptor enhances interleukin 2 production upon antigen stimulation in a T-cell line.
Phospholipase C-gamma 1 (PLC gamma 1) plays an important role in the signal transduction pathway by producing second messengers. However, the activation mechanism of PLC gamma 1 and the role of the phosphatidylinositol pathway for interleukin 2 (IL-2) production in T lymphocytes remain to be determined. To analyze the functional role of this pathway in T cells, we expressed an epidermal growth factor receptor (EGF) or platelet-derived growth factor (PDGF) receptor (EGF-R or PDGF-R), both of which are known to directly activate PLC gamma 1 in fibroblasts, into a murine T-cell hybridoma. Both receptors were expressed on the cell surface and caused tyrosine phosphorylation of multiple substrates, including the receptor itself, upon ligand binding. While EGF stimulation did not either cause phosphorylation of PLC gamma 1 or induce Ca2+ mobilization in the EGF-R transfectant in this system, PDGF treatment induced tyrosine phosphorylation of PLC gamma 1 and Ca2+ mobilization in the PDGF-R transfectant. Stimulation through PDGF-R enhanced IL-2 production upon antigen stimulation of the transfectants, although PDGF treatment alone did not induce IL-2 production. These results suggest that activation of the phosphatidylinositol pathway affects the downstream pathway to IL-2 production but is not sufficient to produce IL-2 and that cooperation with signals from tyrosine kinase cascades is required for IL-2 production.
Nakano
H
H
Division of Molecular Genetics, School of Medicine, Chiba University, Japan.
Ohno
H
H
Saito
T
T
D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007376:Interleukin-2; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D000077214:Becaplermin; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases