Plasma membrane rafts and chaperones in cytokine/STAT signaling.
Plasma membrane rafts and chaperones in cytokine/STAT signaling.
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DOI：
10.18388/abp.2003_3652
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发表时间：
2003
影响因子：
1.7
通讯作者：
P. Sehgal
中科院分区：
文献类型：
--
作者：
P. Sehgal
我们和其他人最近获得的数据表明，在许多不同类型的细胞中，细胞因子-STAT信号是一种伴随通路，起始于被称为“RAFT”的专门化质膜微域(“RAFT-STAT信号假说”)。这些发现具有广泛的意义，因为所有的细胞因子和生长因子都通过与各自的细胞表面受体相互作用来启动靶细胞中的信号传递。新的数据表明，RAFT微域代表了细胞表面的功能单位，通过这些单位，配体刺激的STAT信号被启动。此外，最近的证据表明，伴侣蛋白参与调节STAT信号通路。这些伴侣包括肿瘤想象盘1蛋白(HTid1)的人类同系物，它在质膜水平与Janus kinase2(JAK2)相关，热休克蛋白90(HSP90)在含有小窝蛋白-1的RAFT和细胞质复合体中与STAT3和STAT1蛋白结合，以及葡萄糖调节蛋白58(GRP58/ER-60/ERp57)，它是一种硫醇依赖的蛋白质-二硫键异构酶，在胞浆和RAFT组分中发现与STAT3“statosome”复合体相关。我们认为，在发热的情况下，HSP90伴侣系统在保存肝细胞中的IL-6/STAT3信号方面起着作用。与木筏和胞浆复合体中的特定STAT物种相关的蛋白质伙伴的鉴定和功能，以及细胞因子激活的STATs从木筏的胞浆表面有效地偏离到细胞核中，目前是活跃研究的领域。
We and others have recently obtained data suggesting that cytokine-STAT signaling in many different cell-types is a chaperoned pathway initiated at the level of specialized plasma membrane microdomains called "rafts" (the "raft-STAT signaling hypothesis"). These findings are of broad significance in that all cytokines and growth factors initiate signaling in target cells by interacting with respective cell-surface receptors. The new data suggest that raft microdomains represent the units of function at the cell-surface through which ligand-stimulated STAT signaling is initiated. Moreover, recent evidence shows the involvement of chaperone proteins in regulating the STAT signaling pathway. These chaperones include the human homolog of the tumorous imaginal disc 1 protein (hTid1) which associates with Janus kinase 2 (JAK2) at the level of the plasma membrane, heat shock protein 90 (HSP90) which associates with STAT3 and STAT1 proteins in caveolin-1-containing raft and cytoplasmic complexes, and glucose regulated protein 58 (GRP58/ER-60/ERp57), a thiol dependent protein-disulfide isomerase, found in association with STAT3 "statosome" complexes in the cytosol and in the raft fraction. We suggest a function of the HSP90 chaperone system in preserving IL-6/STAT3 signaling in liver cells in the context of fever. The identification and function of protein partners associated with specific STAT species in rafts and in cytosolic complexes, and in the efficient departure of cytokine-activated STATs from the cytosolic face of rafts towards the cell nucleus are now areas of active investigation.