Golgi reassembly stacking protein 55 interacts with membrane-type (MT) 1-matrix metalloprotease (MMP) and furin and plays a role in the activation of the MT1-MMP zymogen
| Autor: | Christian Roghi, Louise Jones, William R. English, Gillian Murphy, M J Gratian |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Proteases
Viral matrix protein biology Signal transducing adaptor protein macromolecular substances Cell Biology Golgi reassembly Golgi apparatus Matrix metalloproteinase Biochemistry Cell biology symbols.namesake stomatognathic system Zymogen embryonic structures biology.protein symbols Molecular Biology Furin |
| Zdroj: | FEBS Journal. 277:3158-3175 |
| ISSN: | 1742-464X |
| DOI: | 10.1111/j.1742-4658.2010.07723.x |
| Popis: | Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a proteinase involved in the remodelling of extracellular matrix and the cleavage of a number of substrates. MT1-MMP is synthesized as a zymogen that requires intracellular post-translational cleavage to gain biological activity. Furin, a member of the pro-protein convertase family, has been implicated in the proteolytic removal of the MT1-MMP prodomain sequence. In the present study, we demonstrate a role for the peripheral Golgi matrix protein GRASP55 in the furin-dependent activation of MT1-MMP. MT1-MMP and furin were found to co-localize with Golgi reassembly stacking protein 55 (GRASP55). Further analysis revealed that GRASP55 associated with the cytoplasmic domain of both proteases and that the LLY(573) motif in the MT1-MMP intracellular domain was crucial for the interaction with GRASP55. Overexpression of GRASP55 was found to enhance the formation of a complex between MT1-MMP and furin. Finally, we report that disruption of the interaction between GRASP55 and furin led to a reduction in pro-MT1-MMP activation. Taken together, these data suggest that GRASP55 may function as an adaptor protein coupling MT1-MMP with furin, thus leading to the activation of the zymogen. |
| Databáze: | OpenAIRE |
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