Mutation of a cleavage site adjacent to the mature domain leads to increase in secreted mature BMP-2 with reduced activity
| Autor: | Aileen J Zhou, Zhining Zhu, Sean A.F. Peel, Cameron M L Clokie |
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| Rok vydání: | 2012 |
| Předmět: |
Cleavage factor
Molecular Sequence Data Clinical Biochemistry Bone Morphogenetic Protein 2 Enzyme-Linked Immunosorbent Assay CHO Cells Biology Cleavage (embryo) Bone morphogenetic protein Polymerase Chain Reaction Mice Endocrinology Cricetinae Animals Humans Protein Isoforms Secretion Amino Acid Sequence Sequence Homology Amino Acid Wild type Biological activity Cell Biology Proprotein convertase Molecular biology Protein Structure Tertiary HEK293 Cells Gene Expression Regulation Cell culture Mutation Peptides |
| Zdroj: | Growth Factors. 30:267-275 |
| ISSN: | 1029-2292 0897-7194 |
| DOI: | 10.3109/08977194.2012.686497 |
| Popis: | Proteolytic cleavage of precursor bone morphogenetic protein (proBMP) is an important step in generating the active mature BMP. ProBMP-2 contains two proprotein convertase (PC) recognition sites (S1 and S2) and is postulated to be cleaved by PCs at those sites. Cell lines expressing proBMP-2, with a silenced S1 site (mS1) that inhibited PC cleavage, secreted the 20-kDa form BMP-2, while cells expressing wild type (wt) BMP-2 secreted 18- and 20-kDa mature BMP-2 N-terminal isoforms. The mS1 cells secreted 15-fold more mature BMP-2 than the wt, despite their similar mRNA levels. Mutant-secreted BMP-2 demonstrated biological activity in vitro; however, its activity was reduced compared with wt. These data demonstrate that proBMP-2 can be cleaved at an alternative cleavage site without prior S1 site cleavage in cell lines overexpressing BMP-2 and more importantly suggest that the presence of the 2-kDa linker peptide can affect activity and secretion of the mature protein. |
| Databáze: | OpenAIRE |
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