You're going to need a bigger (glass bottom) boat.
Sci Signal
; 5(218): pe14, 2012 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-22472647
ABSTRACT
Signaling molecules of the transforming growth factor (TGF)-ß family are generated from proprotein precursors containing prodomain sequences that are typically removed to allow signaling by the mature ligands. A form of a TGF-ß family ligand that remains covalently attached to its prodomain but retains signaling activity has been identified. Glass bottom boat (Gbb), a Drosophila homolog of the bone morphogenetic protein 5/6/7/8 subfamily, is active as a carboxyl-terminal fragment of the proprotein (Gbb15) that is generated by a conventional processing event common to TGF-ß ligands. Unexpectedly, a larger form (Gbb38) produced by processing at a newly identified furin site in the prodomain is also secreted and active. Contrary to the present paradigm in which TGF-ß ligands require dissociation of the entire prodomain for activity, Gbb38 is active in cell culture and in vivo without additional processing at conventional sites. The large form can restore the viability of gbb mutant animals but has distinct signaling properties compared with the conventional form. Production of multiple functional ligands from one proprotein is a potential mechanism to fine-tune TGF-ß signaling outputs. Mutations in TGF-ß family members have been linked to human diseases, several of which affect potential furin cleavage sites in prodomains. However, given the diversity of potential furin processing sites and prodomain functions, direct experimentation will be required to determine whether production of active jumbo ligands is a general feature of TGF-ß superfamily members.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursores de Proteínas
/
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Proteínas de Drosophila
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Signal
Assunto da revista:
CIENCIA
/
FISIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos