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001-es BibID:BIBFORM044572
Első szerző:Nagy Péter (biofizikus)
Cím:Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy / Péter Nagy, Attila Jenei, Achim K. Kirsch, János Szöllősi, Sándor Damjanovich, Thomas M. Jovin
Dátum:1999
Megjegyzések: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 microm 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 microm, 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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animal
antagonists and inhibitors
chemistry
Cho Cells
Enzyme Activation
Enzyme Inhibitors
Hamsters
Human
metabolism
methods
Microscopy
Microscopy, Atomic Force
Microscopy, Confocal
pharmacology
Quinazolines
Receptor Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Support, Non-U.S.Gov't
Tumor Cells, Cultured
egyetemen (Magyarországon) készült közlemény
Megjelenés:Journal of Cell Science 112 : Pt 11 (1999), p. 1733-1741. -
További szerzők:Jenei Attila (1966-) (biofizikus) Kirsch, Achim K. Szöllősi János (1953-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus) Jovin, Thomas M.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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