Wirthmueller U, Kurosaki T, Murakami M S, Ravetch J V
DeWitt Wallace Research Laboratory, Sloan-Kettering Institute, New York, New York 10021.
J Exp Med. 1992 May 1;175(5):1381-90. doi: 10.1084/jem.175.5.1381.
To determine the functional role of the two isoforms of Fc gamma RIII (CD16) (IIIA, IIIB), the signal transduction capabilities of wild-type and mutant forms of these receptors were analyzed in transfected lymphoid, myeloid, and fibroblastic cell lines. Functional reconstitution of receptor signalling was observed in hematopoietic T and mast cells, and was absent in nonhematopoietic (CHO) cells. Fc gamma RIIIA, a hetero-oligomeric receptor composed of a ligand-binding subunit alpha and dimeric gamma chains, generated both proximal and distal responses in Jurkat and P815 cells, typical of what is seen in natural killer cells and macrophages upon receptor activation. In contrast, Fc gamma RIIIB, which is normally attached to the cell surface via a glycosyl-phosphatidylinositol anchor, was incapable of transducing signals. After crosslinking, Fc gamma RIIIA signalling was dependent only upon the gamma chain. Fc gamma RIIIA chimeras in which the alpha subunit transmembrane and cytoplasmic domains were substituted with the corresponding gamma chain sequences functioned as well as wild-type hetero-oligomeric receptors. These data indicate that the ability of the Fc gamma RIIIA complex to activate the appropriate pathways for cell activation is cell-type restricted and independent of the transmembrane and cytoplasmic domains of the alpha subunit. The presence of the gamma chain is responsible for the assembly of, as well as the signal transduction by, the functional cell surface complex.
为确定FcγRIII(CD16)的两种同种型(IIIA、IIIB)的功能作用,在转染的淋巴细胞系、髓细胞系和成纤维细胞系中分析了这些受体野生型和突变型的信号转导能力。在造血T细胞和肥大细胞中观察到受体信号传导的功能重建,而在非造血(CHO)细胞中则未观察到。FcγRIIIA是一种由配体结合亚基α和二聚体γ链组成的异源寡聚体受体,在Jurkat细胞和P815细胞中产生近端和远端反应,这是自然杀伤细胞和巨噬细胞受体激活时典型的反应。相比之下,通常通过糖基磷脂酰肌醇锚定附着在细胞表面的FcγRIIIB无法转导信号。交联后,FcγRIIIA信号传导仅依赖于γ链。其中α亚基跨膜和胞质结构域被相应γ链序列取代的FcγRIIIA嵌合体的功能与野生型异源寡聚体受体相同。这些数据表明,FcγRIIIA复合物激活细胞激活适当途径的能力受细胞类型限制,且独立于α亚基的跨膜和胞质结构域。γ链的存在负责功能性细胞表面复合物的组装以及信号转导。