Prodomains regulate the synthesis, extracellular localisation and activity of TGF-ß superfamily ligands.
Growth Factors
; 29(5): 174-86, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21864080
ABSTRACT
All transforming growth factor-ß (TGF-ß) ligands are synthesised as precursor molecules consisting of a signal peptide, an N-terminal prodomain and a C-terminal mature domain. During synthesis, prodomains interact non-covalently with mature domains, maintaining the molecules in a conformation competent for dimerisation. Dimeric precursors are cleaved by proprotein convertases, and TGF-ß ligands are secreted from the cell non-covalently associated with their prodomains. Extracellularly, prodomains localise TGF-ß ligands within the vicinity of their target cells via interactions with extracellular matrix proteins, including fibrillin and perlecan. For some family members (TGF-ß1, TGF-ß2, TGF-ß3, myostatin, GDF-11 and BMP-10), prodomains bind with high enough affinity to suppress biological activity. The subsequent mechanism of activation of these latent TGF-ß ligands varies according to cell type and context, but all activating mechanisms directly target prodomains. Thus, prodomains control many aspects of TGF-ß superfamily biology, and alterations in prodomain function are often associated with disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Matriz Extracelular
/
Proteínas da Superfamília de TGF-beta
Limite:
Humans
Idioma:
En
Revista:
Growth Factors
Assunto da revista:
BIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM