Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.
J Biol Chem
; 295(9): 2687-2697, 2020 02 28.
Article
em En
| MEDLINE
| ID: mdl-31988245
Microfibril-associated glycoprotein-1 (MAGP-1) is a component of vertebrate extracellular matrix (ECM) microfibrils that, together with the fibrillins, contributes to microfibril function. Many of the phenotypes associated with MAGP-1 gene inactivation are consistent with dysregulation of the transforming growth factor ß (TGFß)/bone morphogenetic protein (BMP) signaling system. We have previously shown that full-length MAGP-1 binds active TGFß-1 and some BMPs. The work presented here further defines the growth factor-binding domain of MAGP-1. Using recombinant domains and synthetic peptides, along with surface plasmon resonance analysis to measure the kinetics of the MAGP-1-TGFß-1 interaction, we localized the TGFß- and BMP-binding site in MAGP-1 to a 19-amino acid-long, highly acidic sequence near the N terminus. This domain was specific for binding active, but not latent, TGFß-1. Growth factor activity experiments revealed that TGFß-1 retains signaling activity when complexed with MAGP-1. Furthermore, when bound to fibrillin, MAGP-1 retained the ability to interact with TGFß-1, and active TGFß-1 did not bind fibrillin in the absence of MAGP-1. The absence of MAGP was sufficient to raise the amount of total TGFß stored in the ECM of cultured cells, suggesting that the MAGPs compete with the TGFß large latent complex for binding to microfibrils. Together, these results indicate that MAGP-1 plays an active role in TGFß signaling in the ECM.
Palavras-chave
MFAP2; TGFß; bone morphogenetic protein (BMP); cell signaling; extracellular cellular matrix (ECM); extracellular matrix; fibrillar; fibrillin; growth factor; growth factor signaling; microfibril; microfibril associated glycoprotein (MAGP); protein-protein interaction; transforming growth factor beta (TGFß)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta1
/
Fatores de Processamento de RNA
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2020
Tipo de documento:
Article