Mapping ErbB receptors on breast cancer cell membranes during signal transduction
Author:
Yang Shujie1, Raymond-Stintz Mary Ann1, Ying Wenxia2, Zhang Jun3, Lidke Diane S.1, Steinberg Stanly L.2, Williams Lance3, Oliver Janet M.1, Wilson Bridget S.1
Affiliation:
1. Department of Pathology and Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA 2. Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM 87131, USA 3. Department of Computer Science, University of New Mexico, Albuquerque, NM 87131, USA
Abstract
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.
Publisher
The Company of Biologists
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