Dominant negative mutants of transforming growth factor-beta 1 inhibit the secretion of different transforming growth factor-beta isoforms.
AUTOR(ES)
Lopez, A R
RESUMO
Transforming growth factor-beta (TGF-beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. Several related isoforms have been structurally characterized, three of which, TGF-beta 1, -beta 2, and -beta 3, have been detected in mammalian cells and tissues. Each TGF-beta form is a homodimer of a 112-amino-acid polypeptide which is encoded as a larger polypeptide precursor. We have introduced several mutations in the TGF-beta 1 precursor domain, resulting in an inhibition of TGF-beta 1 secretion. Coexpression of these mutants with wild-type TGF-beta 1, -beta 2, and -beta 3 results in a competitive and specific inhibition of the secretion of different TFG-beta forms, indicating that these mutated versions act as dominant negative mutants for TGF-beta secretion. Overexpression of dominant negative mutants can thus be used to abolish endogenous secretion of TGF-beta and structurally related family members, both in vitro and in vivo, and to probe in this way the physiological functions of the members of the TGF-beta superfamily.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=369610Documentos Relacionados
- Secretion and transcriptional regulation of transforming growth factor-beta 3 during myogenesis.
- Transforming growth factor-beta complexes with thrombospondin.
- Nucleotide sequence of chicken transforming growth factor-beta 1 (TGF-beta 1).
- Sequence of the porcine transforming growth factor-beta precursor.
- Tumour-stromal interactions: Transforming growth factor-beta isoforms and hepatocyte growth factor/scatter factor in mammary gland ductal morphogenesis