دورية أكاديمية
Termination of tyrphostin AG1478 application results in different recovery of EGF receptor tyrosine residues 1045 and 1173 phosphorylation in A431 cells.
| العنوان: | Termination of tyrphostin AG1478 application results in different recovery of EGF receptor tyrosine residues 1045 and 1173 phosphorylation in A431 cells. |
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| المؤلفون: | Kondratov KA; Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Avenue 4, St Petersburg 194064, Russia., Chernorudskiy AL, Amosova AP, Kornilova ES |
| المصدر: | Cell biology international [Cell Biol Int] 2009 Dec 16; Vol. 34 (1), pp. 81-7. Date of Electronic Publication: 2009 Dec 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Chichester Country of Publication: England NLM ID: 9307129 Publication Model: Electronic Cited Medium: Internet ISSN: 1095-8355 (Electronic) Linking ISSN: 10656995 NLM ISO Abbreviation: Cell Biol Int Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2013- : John Wiley & Sons Chichester : Original Publication: London, UK : Published for the International Federation for Cell Biology by Academic Press, c1993- |
| مواضيع طبية MeSH: | ErbB Receptors/*metabolism , Tyrosine/*metabolism , Tyrphostins/*pharmacology, Cell Line, Tumor ; Endocytosis ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/chemistry ; Humans ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-cbl/metabolism ; Quinazolines ; Ubiquitination |
| مستخلص: | Tyrphostin AG1478 is known as a specific and reversible inhibitor of TK (tyrosine kinase) activity of the EGFR [EGF (epidermal growth factor) receptor]. It is attractive as an anticancer agent for cancers with elevated EGFR TK levels. However, post-application effects of AG1478 are not well studied. We have analysed EGFR phosphorylation after termination of AG1478 application using human epidermoid carcinoma A431 cells. It was found that AG1478 inhibitory action is fast, but not fully reversible: removal of tyrphostin resulted in incomplete restoration of the overall EGFR phosphorylation. Analysing the state of two individual autophosphorylation sites of internalized EGFR, Tyr1045 and Tyr1173, we demonstrated that phosphorylation of Tyr1173 involved in stimulation of the MAPK (mitogen-activated protein kinase) cascade was restored much more efficiently than that in position 1045, which binds the ubiquitin ligase c-Cbl and is necessary for targeting the receptor for lysosomal degradation. c-Cbl association with EGFR abolished by AG1478 was not reestablished after tyrphostin cessation. As a consequence, ubiquitination-dependent EGFR delivery to lysosomes was blocked, while phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) was even increased. Thus, after termination of AG1478, the intracellular level of the inhibitor can be reached at which mitogenic signalling will be restored, whereas the EGFR negative regulation due to lysosomal degradation will not. |
| المشرفين على المادة: | 0 (Quinazolines) 0 (Tyrphostins) 170449-18-0 (RTKI cpd) 42HK56048U (Tyrosine) EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl) EC 2.7.10.1 (ErbB Receptors) EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) |
| تواريخ الأحداث: | Date Created: 20091202 Date Completed: 20100504 Latest Revision: 20181201 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1042/CBI20090159 |
| PMID: | 19947936 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-8355 |
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| DOI: | 10.1042/CBI20090159 |