当前位置: X-MOL 学术Sci. Signal. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
CD45 exclusion- and cross-linking-based receptor signaling together broaden FcεRI reactivity.
Science Signaling ( IF 7.3 ) Pub Date : 2018-12-18 , DOI: 10.1126/scisignal.aat0756
James H Felce 1, 2, 3 , Erdinc Sezgin 1 , Madina Wane 1, 2 , Heather Brouwer 1, 2 , Michael L Dustin 3 , Christian Eggeling 1 , Simon J Davis 1, 2
Affiliation  

For many years, the high-affinity receptor for immunoglobulin E (IgE) FcεRI, which is expressed by mast cells and basophils, has been widely held to be the exemplar of cross-linking (that is, aggregation dependent) signaling receptors. We found, however, that FcεRI signaling could occur in the presence or absence of receptor cross-linking. Using both cell and cell-free systems, we showed that FcεRI signaling was stimulated by surface-associated monovalent ligands through the passive, size-dependent exclusion of the receptor-type tyrosine phosphatase CD45 from plasma membrane regions of FcεRI-ligand engagement. Similarly to the T cell receptor, FcεRI signaling could also be initiated in a ligand-independent manner. These data suggest that a simple mechanism of CD45 exclusion-based receptor triggering could function together with cross-linking-based FcεRI signaling, broadening mast cell and basophil reactivity by enabling these cells to respond to both multivalent and surface-presented monovalent antigens. These findings also strengthen the case that a size-dependent, phosphatase exclusion-based receptor triggering mechanism might serve generally to facilitate signaling by noncatalytic immune receptors.

中文翻译:

基于 CD45 排斥和交联的受体信号传导共同拓宽了 FcεRI 反应性。

多年来,由肥大细胞和嗜碱性粒细胞表达的免疫球蛋白 E (IgE) FcεRI 的高亲和力受体已被广泛认为是交联(即聚集依赖性)信号受体的典范。然而,我们发现 FcεRI 信号传导可能在存在或不存在受体交联的情况下发生。使用细胞和无细胞系统,我们发现 FcεRI 信号传导受到表面相关单价配体的刺激,通过 FcεRI 配体接合的质膜区域中受体型酪氨酸磷酸酶 CD45 的被动、尺寸依赖性排除。与 T 细胞受体类似,FcεRI 信号传导也可以不依赖配体的方式启动。这些数据表明,基于 CD45 排斥的受体触发的简单机制可以与基于交联的 FcεRI 信号传导一起发挥作用,通过使肥大细胞和嗜碱性粒细胞对多价和表面呈递的单价抗原都有反应,从而扩大肥大细胞和嗜碱性粒细胞的反应性。这些发现还强化了这样一种情况,即大小依赖性、基于磷酸酶排斥的受体触发机制可能通常有助于促进非催化免疫受体的信号传导。
更新日期:2018-12-19
down
wechat
bug