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Mapping ErbB receptors on breast cancer cell membranes during signal transduction
Journal article   Open access   Peer reviewed

Mapping ErbB receptors on breast cancer cell membranes during signal transduction

Shujie Yang, Mary Ann Raymond-Stintz, Wenxia Ying, Jun Zhang, Diane S Lidke, Stanly L Steinberg, Lance Williams, Janet M Oliver and Bridget S Wilson
Journal of cell science, Vol.120(Pt 16), pp.2763-2773
08/15/2007
DOI: 10.1242/jcs.007658
PMID: 17652160
url
https://doi.org/10.1242/jcs.007658View
Published (Version of record) Open Access

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.
Transfection Receptor, Epidermal Growth Factor - ultrastructure Receptor, ErbB-3 - metabolism Cricetulus Humans Receptor, ErbB-2 - metabolism Phosphatidylinositol 3-Kinases - metabolism Protein Transport - drug effects Phosphotyrosine - metabolism STAT5 Transcription Factor - metabolism Breast Neoplasms - enzymology Receptor, Epidermal Growth Factor - metabolism Female Cell Membrane - drug effects CHO Cells Shc Signaling Adaptor Proteins Breast Neoplasms - ultrastructure Cricetinae Receptor, ErbB-2 - ultrastructure Cell Membrane - ultrastructure Neuregulin-1 - pharmacology Receptor Protein-Tyrosine Kinases - metabolism Cell Membrane - enzymology Animals Src Homology 2 Domain-Containing, Transforming Protein 1 Signal Transduction - drug effects Receptor, ErbB-3 - ultrastructure Epidermal Growth Factor - pharmacology Adaptor Proteins, Signal Transducing - metabolism

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