Mapping ErbB receptors on breast cancer cell membranes during signal transduction.
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.
Yang
Shujie
S
Department of Pathology and Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA.
Raymond-Stintz
Mary Ann
MA
Ying
Wenxia
W
Zhang
Jun
J
Lidke
Diane S
DS
Steinberg
Stanly L
SL
Williams
Lance
L
Oliver
Janet M
JM
Wilson
Bridget S
BS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000648:ultrastructure; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D020890:Neuregulin-1 / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism / Q000648:ultrastructure; D020893:Receptor, ErbB-3 / Q000378:metabolism / Q000648:ultrastructure; D050799:STAT5 Transcription Factor / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020890:Neuregulin-1; D019869:Phosphatidylinositol 3-Kinases; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D050799:STAT5 Transcription Factor; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C528024:SHC1 protein, human