Spatial Raft Coalescence Represents an Initial Step in FcγR Signaling1
Spatial Raft Coalescence Represents an Initial Step in FcγR Signaling1
复制标题
空间筏合并代表 FcγR 信号传导的初始步骤1
作者：
H. Kono;Takeshi Suzuki;Kazuhiko Yamamoto;M. Okada;Tadashi Yamamoto;Z. Honda
表征的脂筏作为分离的膜微区组成的异质性蛋白质，这表明在Ag受体交联后的筏的横向组装代表最早的信号产生过程。根据这一概念，交联的Ag受体已被证明与洗涤剂不溶性筏级分没有Src家族激酶的帮助。然而，它还没有建立空间筏合并是否也可以之前Src家族激酶激活。在这项研究中，我们发现在RAW 264.7巨噬细胞中低亲和力FcγR交联后的空间筏聚结不依赖于Src家族激酶活性。发现侧向筏组装归因于配体结合亚基的作用，而不是基于免疫受体酪氨酸的活化基序的信号亚基，因为在大鼠嗜碱性白血病细胞中表达的单体鼠FcγRIIb在交联后成功诱导了空间筏重组。我们还发现FcγRIIb的胞外和跨膜区足以稳定筏。此外，该受体片段以对Src家族激酶抑制和胆固醇消耗敏感的方式触发快速钙动员和用于激活T细胞磷酸化的接头。基于免疫受体酪氨酸的抑制基序和基于免疫受体酪氨酸的激活基序的受体片段的存在下，废除和增强的反应，分别，但不影响筏稳定。这些研究结果支持的概念，配体结合亚基是负责筏聚结，这一事件触发初始的生化信号。
Characterization of lipid rafts as separated membrane microdomains consist of heterogeneous proteins suggesting that lateral assembly of rafts after Ag receptor cross-linking represents the earliest signal generating process. In line with the concept, cross-linked Ag receptors have been shown to associate with detergent-insoluble raft fraction without the aid of Src family kinases. However, it has not been established whether spatial raft coalescence could also precede Src family kinase activation. In this study, we showed that spatial raft coalescence after low-affinity FcγR cross-linking in RAW264.7 macrophages is independent of Src family kinase activity. The lateral raft assembly was found to be ascribed to the action of ligand-binding subunits, rather than to immunoreceptor tyrosine-based activation motif-bearing signal subunits, because monomeric murine FcγRIIb expressed in rat basophilic leukemia cells successfully induced spatial raft reorganization after cross-linking. We also showed that extracellular and transmembrane region of FcγRIIb is sufficient for raft stabilization. Moreover, this receptor fragment triggers rapid calcium mobilization and linker for activation of T cells phosphorylation, in a manner sensitive to Src family kinase inhibition and to cholesterol depletion. Presence of immunoreceptor tyrosine-based inhibitory motif and addition of immunoreceptor tyrosine-based activation motif to the receptor fragment abolished and enhanced the responses, respectively, but did not affect raft stabilization. These findings support the concept that ligand-binding subunit is responsible for raft coalescence, and that this event triggers initial biochemical signaling.
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DOI：
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发表时间：
2001
期刊：
--
影响因子：
--
作者：
P. Cheng;B. Brown;Wenxia Song;S. Pierce
通讯作者：
P. Cheng;B. Brown;Wenxia Song;S. Pierce
影响因子：
32.4
作者：
R. Xavier;Todd Brennan;Qingqin Li;Christine McCormack;B. Seed
通讯作者：
R. Xavier;Todd Brennan;Qingqin Li;Christine McCormack;B. Seed
影响因子：
32.4
作者：
Fu, C;Turck, CW;Chan, AC
通讯作者：
Chan, AC
影响因子：
32.4
作者：
Moran, M;Miceli, MC
通讯作者：
Miceli, MC