Egeblad, M., Mortensen, O. H., van Kempen, L. C., Jaattela, M. (February 2001) BIBX1382BS, but not AG1478 or PD153035, inhibits the ErbB kinases at different concentrations in intact cells. Biochemical and biophysical research communications, 281 (1). pp. 25-31. ISSN 0006-291X (Print)0006-291x
Abstract
The activation of ErbB tyrosine kinase receptors (ErbB1, -2, -3, and -4) by ligand-induced homo- or heterodimerization regulates cell growth, death, and differentiation. AG1478 and PD153035 (also know as AG1517) have been adopted as specific ErbB1 inhibitors based on their high specificity for ErbB1 as compared to ErbB2 in in vitro kinase assays. We compared their ability to inhibit ErbB receptor signaling in intact cells to that of a novel ErbB receptor kinase inhibitor, BIBX1382BS. Neither AG1478 nor PD153035 displayed any specificity for ErbB1-mediated signaling induced by transforming growth factor alpha (TGF-alpha) as compared to signaling initiated through the other ErbB kinases. In contrast, BIBX1382BS was more potent at inhibiting signaling induced by TGF-alpha than that induced by neuregulin1-beta1 or anti-ErbB2 agonist antibodies. Interestingly, this compound blocked antibody-induced ErbB4 homodimer activation at even lower concentrations than ErbB1-triggered signaling. Thus, BIBX1382BS, but not AG1478 and PD153035, can be employed to differentiate between the ErbB kinases in intact cells when used at appropriate concentrations.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Antineoplastic Agents/*pharmacology Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors/*pharmacology Humans Immunoblotting Ligands Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/metabolism Neuregulin-1/metabolism *Organic Chemicals Phosphorylation Quinazolines/*pharmacology Receptor, Epidermal Growth Factor/*antagonists & inhibitors Receptor, erbB-2/antagonists & inhibitors Recombinant Proteins/metabolism Signal Transduction/drug effects Time Factors Transforming Growth Factor alpha/metabolism Tumor Cells, Cultured Tyrphostins/*pharmacology |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ErbB bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase |
| CSHL Authors: | |
| Communities: | CSHL labs > Egeblad lab |
| Depositing User: | Matt Covey |
| Date: | 16 February 2001 |
| Date Deposited: | 05 Dec 2014 16:34 |
| Last Modified: | 05 Dec 2014 16:34 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30953 |
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