Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence.
Science
; 249(4976): 1567-70, 1990 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-1699274
ABSTRACT
Heparin-binding growth factor-1 (HBGF-1) is an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro and remains biologically active after truncation of the amino-terminal domain (HBGF-1 alpha) of the HBGF-1 beta precursor. Polymerase chain reaction mutagenesis and prokaryotic expression systems were used to prepare a mutant of HBGF-1 alpha lacking a putative nuclear translocation sequence (amino acid residues 21 to 27; HBGF-1U). Although HBGF-1U retains its ability to bind to heparin, HBGF-1U fails to induce DNA synthesis and cell proliferation at concentrations sufficient to induce intracellular receptor-mediated tyrosine phosphorylation and c-fos expression. Attachment of the nuclear translocation sequence from yeast histone 2B at the amino terminus of HBGF-1U yields a chimeric polypeptide (HBGF-1U2) with mitogenic activity in vitro and indicates that nuclear translocation is important for this biological response.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator 1 de Crescimento de Fibroblastos
/
Mutação
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
1990
Tipo de documento:
Article