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001-es BibID:	BIBFORM004713
035-os BibID:	(scopus)0037112996 (wos)000179662300005
Első szerző:	Nagy Péter (biofizikus)
Cím:	Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2 / Nagy, P., Vereb, G., Sebestyen, Z., Horvath, G., Lockett, S. J., Damjanovich, S., Park, J. W., Jovin, T. M., Szollosi, J.
Dátum:	2002
Megjegyzések:	The ErbB family of transmembrane receptor tyrosine kinases plays an important role in the pathogenesis of many cancers. The four members of the family, ErbB1-4, form various homo- and heterodimers during the course of signal transduction. A second hierarchical level of molecular associations involving 10(2)-10(3) molecules, termed large-scale clustering, has also been identified, but the regulatory factors and biological consequences of such structures have not been systematically evaluated. In this report, we describe the states of association of ErbB2 and their relationship to local ErbB3 density and lipid rafts based on quantitative fluorescence microscopy of SKBR-3 breast cancer cells. Clusters of ErbB2 colocalized with lipid rafts identified by the GM1-binding B subunit of cholera toxin. Pixel-by-pixel analysis of fluorescence resonance energy transfer between labeled antibodies indicated that the homoassociation (homodimerization) of ErbB2 was proportional to the local density of ErbB2 and inversely proportional to that of ErbB3 and of the raft-specific lipid GM1. Crosslinking lipid rafts with the B subunit of cholera toxin caused dissociation of the rafts and ErbB2 clusters, an effect that was independent of the cytoskeletal anchoring of ErbB2. Crosslinking also decreased ErbB2-ErbB3 heteroassociation and the EGF- and heregulin-induced tyrosine phosphorylation of Shc. When cells were treated with the anti-ErbB2 monoclonal antibody 4D5 (parent murine version of Trastuzumab used in the immunotherapy of breast cancer), internalization of the antibody was inhibited by crosslinking of lipid rafts, but the antiproliferative activity of 4D5 was retained and even enhanced. We conclude that local densities of ErbB2 and ErbB3, as well as the lipid environment profoundly influence the association properties and biological function of ErbB2.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Adaptor Proteins,Signal Transducing Adaptor Proteins,Vesicular Transport analysis Antibodies Antibodies,Monoclonal Antineoplastic Agents Biophysics Breast Neoplasms Carcinoma Cell Division Cell Membrane Cell Transformation,Neoplastic Cells Cholera Toxin Cytoskeletal Proteins Dimerization drug effects Energy Transfer Eukaryotic Cells Female Fluorescence Fluorescence Resonance Energy Transfer genetics Humans Hungary Macromolecular Substances Membrane Microdomains metabolism Microscopy Oncogene Proteins v-erbB pharmacology Phosphorylation physiology Protein Binding Protein-Tyrosine Kinases Proteins Receptor Protein-Tyrosine Kinases Receptor,erbB-2 Receptor,erbB-3 Receptors,Cell Surface Research Signal Transduction Support Tumor Cells,Cultured ultrastructure
Megjelenés:	Journal of Cell Science. - 115 : Pt 22 (2002), p. 4251-4262. -
További szerzők:	Vereb György (1965-) (biofizikus, orvos) Sebestyén Zsolt Horváth Gábor (1974-) (biofizikus) Lockett, Steven J. Damjanovich Sándor (1936-2017) (biofizikus) Park, John W. Jovin, Thomas M. Szöllősi János (1953-) (biofizikus)
Internet cím:	elektronikus változat elektronikus változat
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