DLG1/SAP97 modulates transforming growth factor α bioavailability
| Autor: | Giselle P. de Faria, Etienne Formstecher, Anne-Laure Surena, Jacques Camonis, Marie-Pierre Junier, Jeanne-Marie Studler, Morgane Pidoux, Hervé Chneiweiss, Franck Peiretti |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Tumor suppressor gene
medicine.medical_treatment PDZ domain Biological Availability Fluorescent Antibody Technique CHO Cells ADAM17 Protein Biology Discs Large Homolog 1 Protein Cricetulus ErbB Cell Line Tumor Cricetinae Two-Hybrid System Techniques medicine erbB Animals Humans Protein Precursors Receptor Molecular Biology Adaptor Proteins Signal Transducing EGF Growth factor Membrane Proteins MAGUK Cell Biology Transforming Growth Factor alpha Immunohistochemistry Transmembrane protein Protein Structure Tertiary ADAM Proteins DLG1 Cancer research biology.protein Protein Binding Signal Transduction Transforming growth factor |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (2):264-272 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2008.09.005 |
| Popis: | TGFalpha and its receptor EGFR participate in the development of a wide range of tumors including gliomas, the main adult primary brain tumors. TGFalpha soluble form results from the cleavage by the metalloprotease TACE/ADAM17 of the extracellular part of its transmembrane precursor, pro-TGFalpha. To gain insights into the mechanisms underlying TGFalpha bioavailability, a yeast two-hybrid screen was performed to identify proteins interacting with pro-TGFalpha intracellular domain (ICD). DLG1/SAP97 (Discs Large Gene 1 or Synapse Associated Protein 97) was found to interact with both pro-TGFalpha and TACE ICDs through distinct PDZ domains. An in vivo pro-TGFalpha-DLG1-TACE complex was detected in U251 glioma cells and in gliomas-derived tumor initiating cells. Interaction between DLG1 and TACE diminished in response to stimulations promoting pro-TGFalpha shedding. Manipulation of DLG1 levels revealed dual actions of DLG1 on pro-TGFalpha shedding, favoring approximation of pro-TGFalpha and TACE, while limiting TACE full shedding activity. These results show that DLG1 participates in the control of TGFalpha bioavailability through its dynamic interaction with the growth factor precursor and TACE. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|