ROLE OF ASSOCIATED GAMMA-CHAIN IN TYROSINE KINASE ACTIVATION VIA MURINE FC-GAMMA-RIII

被引:87
作者
BONNEROT, C [1 ]
AMIGORENA, S [1 ]
CHOQUET, D [1 ]
PAVLOVICH, R [1 ]
CHOUKROUN, V [1 ]
FRIDMAN, WH [1 ]
机构
[1] INST PASTEUR,INSERM,U261,NEUROBIOL LAB,F-75724 PARIS 15,FRANCE
关键词
ASSOCIATED-CHAIN; CELL ACTIVATION; FC RECEPTOR; TYROSINE KINASE; PHOSPHORYLATION;
D O I
10.1002/j.1460-2075.1992.tb05340.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Type III receptors for the Fc portion of IgG (Fc-gamma-RIII), initially characterized on macrophages and NK cells, are also expressed on several pre-B cell lines. Surface expression of Fc-gamma-RIII requires the association of the ligand binding alpha-chain with homodimeric gamma-chains. Type II Fc-gamma-R is homologous to Fc-gamma-RIII alpha-chain in the extracellular portion and differs in the transmembrane and cytoplasmic domains. The role of Fc-gamma-R in cell activation was investigated by expressing Fc-gamma-RIII and the lymphocyte-specific b1 isoform of Fc-gamma-RII (Fc-gamma-RIIb1) in an Fc-gamma-R-negative, sIgG-positive B-cell line. We found that, in contrast to Fc-gamma-RIIb1, Fc-gamma-RIII triggers the same events of cell activation as sIgG i.e. Ca2+ mobilization, tyrosine phosphorylation and IL-2 secretion. By expressing cytoplasmic domain-lacking Fc-gamma-RIII alpha-chain in the absence or in the presence of gamma-chains, we demonstrated that cell activation via Fc-gamma-RIII requires the co-expression of gamma-chains, and is independent of the cytoplasmic portion of the alpha-chain. Furthermore, the cytoplasmic portion of the gamma-chain, fused to the extracellular and transmembrane domains of Fc-gamma-RII confers on the chimeric receptor the ability to trigger cell activation. Mutation of one tyrosine residue in the cytoplasmic domain of the gamma-chain prevented triggering of cytoplasmic signals. We therefore demonstrate that a tyrosine-containing motif, present in the cytoplasmic domain of the associated gamma-chain, is necessary and sufficient to trigger cell activation via Fc-gamma-RIII.
引用
收藏
页码:2747 / 2757
页数:11
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