Yang Shujie, Raymond-Stintz Mary Ann, Ying Wenxia, Zhang Jun, Lidke Diane S, Steinberg Stanly L, Williams Lance, Oliver Janet M, Wilson Bridget S
Department of Pathology and Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA.
J Cell Sci. 2007 Aug 15;120(Pt 16):2763-73. doi: 10.1242/jcs.007658. Epub 2007 Jul 24.
Distributions of ErbB receptors on membranes of SKBR3 breast cancer cells were mapped by immunoelectron microscopy. The most abundant receptor, ErbB2, is phosphorylated, clustered and active. Kinase inhibitors ablate ErbB2 phosphorylation without dispersing clusters. Modest co-clustering of ErbB2 and EGFR, even after EGF treatment, suggests that both are predominantly involved in homointeractions. Heregulin leads to dramatic clusters of ErbB3 that contain some ErbB2 and EGFR and abundant PI 3-kinase. Other docking proteins, such as Shc and STAT5, respond differently to receptor activation. Levels of Shc at the membrane increase two- to five-fold with EGF, whereas pre-associated STAT5 becomes strongly phosphorylated. These data suggest that the distinct topography of receptors and their docking partners modulates signaling activities.
通过免疫电子显微镜对SKBR3乳腺癌细胞膜上的表皮生长因子受体（ErbB）分布进行了定位。最丰富的受体ErbB2发生了磷酸化、聚集且具有活性。激酶抑制剂可消除ErbB2的磷酸化，但不会使聚集物分散。即使在表皮生长因子（EGF）处理后，ErbB2和表皮生长因子受体（EGFR）仍有适度的共同聚集，这表明两者主要参与同型相互作用。神经调节蛋白导致ErbB3形成显著的聚集物，其中包含一些ErbB2和EGFR以及大量的磷脂酰肌醇-3激酶（PI 3-激酶）。其他对接蛋白，如生长因子结合蛋白2（Shc）和信号转导子和转录激活子5（STAT5），对受体激活的反应不同。在EGF作用下，膜上的Shc水平增加2至5倍，而预先结合的STAT5则被强烈磷酸化。这些数据表明，受体及其对接伙伴的独特拓扑结构调节了信号传导活性。
