Cross-linking of Fc gamma RIIIA on natural killer cells results in tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2.
The Fc gamma RIIIA, which is composed of a transmembrane IgG-binding glycoprotein and either a disulfide-linked homodimer (zeta zeta, gamma gamma) or heterodimer (zeta gamma), mediates the antibody-dependent cellular cytotoxicity in NK cells. The role of phospholipase C (PLC) isozymes in Fc gamma RIIIA-mediated signal transduction was investigated. The NK cell line NK3.3 was found to contain PLC-gamma 1 and an especially high concentration of PLC-gamma 2, but PLC-beta 1 and PLC-delta 1 were not detected. Cross-linking of Fc gamma RIIIA on NK3.3 cells induced a rapid phosphorylation of PLC-gamma 1 and PLC-gamma 2 on tyrosine residues. Pretreatment of NK3.3 cells with a tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2. These results indicate that activation of Fc gamma RIIIA on NK3.3 cells is coupled either directly or indirectly to a nonreceptor tyrosine kinase, which phosphorylates, and thereby activates PLC-gamma 1 and PLC-gamma 2.
Liao
F
F
Department of Molecular Biology and Genetics, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Shin
H S
HS
Rhee
S G
SG
D016227:Benzoquinones; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D047029:Lactams, Macrocyclic; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D016227:Benzoquinones; D003432:Cross-Linking Reagents; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D011809:Quinones; D017452:Receptors, IgG; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D010738:Type C Phospholipases