Mig-6 Is a Negative Regulator of the Epidermal Growth Factor Receptor Signal
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Peter Oliver Hackel
Abstract
In contrast to signal generation and transmission, the mechanisms and molecules that negatively regulate receptor tyrosine kinase (RTK) signaling are poorly understood. Here we characterize Mig-6 as a novel negative feedback regulator of the epidermal growth factor receptor (EGFR) and potential tumor suppressor. Mig-6 was identified in a yeast twohybrid screen with the kinase active domain of the EGFR as bait. Upon EGF stimulation Mig-6 binds to the EGFR involving a highly acidic region between amino acids 985 995. This interaction is kinase activitydependent, but independent of tyrosine 992. Mig-6 overexpression results in reduced activation of the mitogenactivated protein kinase ERK2 in response to EGF, but not FGF or PDGF, stimulation and in enhanced receptor internalization without affecting the rate of degradation. The induction of Mig-6 mRNA expression in response to EGF, but not FGF, indicates the existence of a negative regulatory feedback loop. Consistent with these findings, a possible role as tumor suppressor is indicated by Mig-6-mediated inhibition of EGFR overexpressioninduced transformation of Rat1 cells.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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- Erratum
- Acknowledgement
- Content Index
- Author Index
- Subject Index
Artikel in diesem Heft
- New Control of Mitochondrial Membrane Potential and ROS Formation A Hypothesis
- Brix from Xenopus laevis and Brx1p From Yeast Define a New Family of Proteins Involved in the Biogenesis of Large Ribosomal Subunits
- Mig-6 Is a Negative Regulator of the Epidermal Growth Factor Receptor Signal
- β-Carotene Inhibits Growth of Human Colon Carcinoma Cells in Vitro by Induction of Apoptosis
- Ligand-Mediated Protection against Phage Lysis as a Positive Selection Strategy for the Enrichment of Epitopes Displayed on the Surface of E. coli Cells
- Structural and Redox Properties of the Leaderless DsbE (CcmG) Protein: Both Active-Site Cysteines of the Reduced Form Are Involved in Its Function in the Escherichia coli Periplasm
- Polyphenols of Cocoa: Inhibition of Mammalian 15-Lipoxygenase
- Total Antioxidant Capacity and Nuclear DNA Damage in Keratinocytes after Exposure to H2 O2
- Recombinant Cryptic Human Fibronectinase Cleaves Actin and Myosin: Substrate Specificity and Possible Role in Muscular Dystrophy
- Rat Tripeptidyl Peptidase I: Molecular Cloning, Functional Expression, Tissue Localization and Enzymatic Characterization
- Determination of NADH in Frozen Rat Brain Sections by Laser-Induced Fluorescence
- Human -Calpain: Simple Isolation from Erythrocytes and Characterization of Autolysis Fragments
- Erratum
- Acknowledgement
- Content Index
- Author Index
- Subject Index
