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  Activation dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy

Nagy, P., Jenei, A., Kirsch, A. K., Szoelloesi, J., Damjanovich, S., & Jovin, T. M. (1999). Activation dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy. Journal of Cell Science, 112, 1733-1741.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-FB3F-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-9CD2-D
Genre: Journal Article

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Nagy, P.1, Author              
Jenei, A.2, Author
Kirsch, A. K.1, Author              
Szoelloesi, J., Author
Damjanovich, S., Author
Jovin, T. M.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              
2Max Planck Society, ou_persistent13              

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Free keywords: Epidermal growth-factor; Human lymphoblastoid-cells; Hla class-i; Monoclonal-antibody; Signal-transduction; Plasma-membrane; Energy-transfer; Breast-cancer; Heregulin; Molecules
 Abstract: ErbB2 (HER2, Neu), a member of the epidermal growth factor (EGF) receptor tyrosine kinase family, is often overexpressed in breast cancer and other malignancies, ErbB2 homodimerizes but also presents as a common auxiliary subunit of the EGF and heregulin receptors (erbB1 or EGFR; and erbB3-4, respectively), with which it heteroassociates, ErbB2 is generally regarded as an orphan (ligand-less) receptor with a very potent kinase domain activated either via its associated partners or constitutively as a consequence of discrete mutations. It follows that the extent and regulation of its cell surface interactions are of central importance. We have studied the large-scale association pattern of erbB2 in quiescent and activated cells labeled with fluorescent anti-erbB2 monoclonal antibodies using scanning near-field optical microscopy (SNOM), ErbB2 was found to be concentrated in irregular membrane patches with a mean diameter of approx. 0.5 mu m in nonactivated SKBR3 and MDA453 human breast tumor cells. The average number of erbB2 proteins in a single cluster on nonactivated SKBR3 cells was about 10(3). Activation of SKBR3 cells with EGF, heregulin as well as a partially agonistic anti-erbB2 monoclonal antibody led to an increase in the mean cluster diameter to 0.6-0.9 mu m, irrespective of the ligand, The EGF-induced increase in the erbB2 cluster size was inhibited by the EGFR-specific tyrosine kinase inhibitor PD153035, The average size of erbB2 clusters on the erbB2-transfected line of CHO cells (CB2) was similar to that of activated SKBR3 cells, a finding correlated with the increased base-line tyrosine phosphorylation of erbB2 in cells expressing only erbB2, We conclude that an increase in cluster size may constitute a general phenomenon in the activation of erbB2.

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Language(s): eng - English
 Dates: 2005-08-161999
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 231791
Other: 11476
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Title: Journal of Cell Science
Source Genre: Journal
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Pages: - Volume / Issue: 112 Sequence Number: - Start / End Page: 1733 - 1741 Identifier: -