Metabolic activation-related CD147-CD98 complex
Metabolic activation-related CD147-CD98 complex
复制标题
DOI：
10.1074/mcp.m400207-mcp200
复制
发表时间：
2005-08-01
影响因子：
7
通讯作者：
Hemler, ME
中科院分区：
文献类型：
--
作者：
Xu, DS;Hemler, ME
细胞表面CD147蛋白促进基质金属蛋白酶和透明质酸的产生，与单羧酸转运体和整合素相关，并参与生殖、神经、炎症和肿瘤功能。在这里，我们结合共价交联、质谱蛋白鉴定和共免疫沉淀来显示CD147与三种主要转运体（CD98重链(CD98hc)- l型氨基酸转运体、ASCT2和单羧酸转运体）以及细胞增殖调节剂（上皮细胞粘附分子）的选择性关联。在这些多组分复合物的组装中，CD147和CD98hc起着中心的组织作用。RNA干扰敲除实验建立了CD147和CD98hc表达之间的密切联系，以及CD147（和CD98hc）与细胞增殖之间的密切正相关。随着CD147-CD98hc复合物和增殖的减少，amp激活的蛋白激酶（细胞“燃料表”）被激活，表明细胞能量代谢受到干扰。我们的数据表明CD147-CD98细胞表面超复合体在能量代谢中起关键作用，可能通过协调乳酸和氨基酸的运输。此外，我们展示了共价交联，以及质谱，可以用来鉴定密切相关的跨膜蛋白。除了与CD98hc和CD147相关的跨膜蛋白外，这种方法也应该适用于许多其他类型的跨膜蛋白。
Cell surface CD147 protein promotes production of matrix metalloproteinases and hyaluronan, associates with monocarboxylate transporters and integrins, and is involved in reproductive, neural, inflammatory, and tumor functions. Here we combined covalent cross-linking, mass spectrometric protein identification, and co-immunoprecipitation to show selective CD147 association with three major types of transporters (CD98 heavy chain (CD98hc)-L-type amino acid transporter, ASCT2, and monocarboxylate transporters) as well as a regulator of cell proliferation ( epithelial cell adhesion molecule). In the assembly of these multicomponent complexes, CD147 and CD98hc play a central organizing role. RNA interference knock-down experiments established a strong connection between CD147 and CD98hc expression and a strong positive association of CD147 ( and CD98hc) with cell proliferation. As the CD147-CD98hc complex and proliferation diminished, AMP-activated protein kinase ( a cellular "fuel gauge") became activated, indicating a disturbance of cellular energy metabolism. Our data point to a CD147-CD98 cell surface supercomplex that plays a critical role in energy metabolism, likely by coordinating transport of lactate and amino acids. Furthermore we showed how covalent cross-linking, together with mass spectrometry, can be used to identify closely associated transmembrane proteins. This approach should also be applicable to many other types of transmembrane proteins besides those associated with CD98hc and CD147.