Proteolytic cleavage of Trop2 at Arg87 is mediated by matriptase and regulated by Val194
| Autor: | Smita D. Mahale, Bhakti R. Pathak, Sanjana Rane, Shaini Joseph, Ananya A. Breed, Pradnya R. Kamble |
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| Rok vydání: | 2020 |
| Předmět: |
Proteolysis
Mutant Biophysics Cleavage (embryo) Arginine Biochemistry 03 medical and health sciences Structure-Activity Relationship Structural Biology Antigens Neoplasm Cell Line Tumor Genetics medicine Humans Matriptase Computer Simulation Homology modeling Amino Acid Sequence Molecular Biology 030304 developmental biology Serine protease chemistry.chemical_classification 0303 health sciences medicine.diagnostic_test biology Chemistry 030302 biochemistry & molecular biology Serine Endopeptidases Valine Cell Biology Transmembrane protein Amino acid HEK293 Cells Amino Acid Substitution Structural Homology Protein Mutation biology.protein Protein Multimerization Cell Adhesion Molecules |
| Zdroj: | FEBS lettersReferences. 594(19) |
| ISSN: | 1873-3468 |
| Popis: | Proteolytic processing is an important post-translational modification affecting protein activity and stability. In the current study, we investigate the N-terminal cleavage of Trop2, a protein which is overexpressed in many cancers. We demonstrate that Trop2 is cleaved at Arg87 by a transmembrane serine protease, matriptase. Homology modeling and site-directed mutagenesis of amino acids in close proximity to the matriptase cleavage site reveal the importance of Val194 in regulating Trop2 cleavage. Co-immunoprecipitation studies confirm that amino acid substitutions at Arg87, Thr88, Lys189, Val194, and His195 do not affect Trop2 dimerization. However, cleavage of wild-type Trop2 by matriptase is inhibited when it is allowed to dimerize with a V194 A mutant monomer, further confirming the role of Val194 in matriptase-mediated N-terminal cleavage. |
| Databáze: | OpenAIRE |
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