| Registro completo |
| Provedor de dados: |
BJMBR
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| País: |
Brazil
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| Título: |
Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro
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| Autores: |
Valiulyte,I.
Preitakaite,V.
Tamasauskas,A.
Kazlauskas,A.
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| Data: |
2018-01-01
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| Ano: |
2018
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| Palavras-chave: |
Semaphorin
Sema3C
HUVEC
Angiogenesis
Furin-like pro-protein convertases
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| Resumo: |
Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein. Several studies have shown that the furin-mediated processing of the basic domain of Sema3F and Sema3A is critical for association with receptors. It is unclear, however, if this mechanism can also be applied to other Sema3 proteins, including the main subject of this study, Sema3C. To address this question, we generated a variant of the full-length human Sema3C carrying point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745, which would disable the processing of Sema3C at this specific location. The effects produced by this mutation were tested in an in vitro angiogenesis assay together with the wild-type Sema3C, Sema3A, and Sema3F proteins. Our results showed that the inhibitory effect of Sema3C on microcapillary formation by human umbilical vein endothelial cells could be abrogated upon mutation at the Sema3C basic domain within putative furin cleavage site 742RNRR745, indicating that this site was essential for the Sema3 biological activity.
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| Tipo: |
Info:eu-repo/semantics/article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018001100610
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| Editor: |
Associação Brasileira de Divulgação Científica
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| Relação: |
10.1590/1414-431x20187786
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| Formato: |
text/html
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| Fonte: |
Brazilian Journal of Medical and Biological Research v.51 n.11 2018
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| Direitos: |
info:eu-repo/semantics/openAccess
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