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.
|Titolo:||Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence|
|Parole Chiave:||Oligonucleotide Probes; Animals; Recombinant Proteins; Transcription, Genetic; Mice; Amino Acid Sequence; Cell Nucleus; Endothelium, Vascular; Receptors, Mitogen; Receptors, Vascular Endothelial Growth Factor; Base Sequence; Cattle; Fibroblast Growth Factor 1; Cells, Cultured; Kinetics; Binding, Competitive; Molecular Sequence Data; Mitogens; Mutation; Cell Line; DNA Replication; Cell Division|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||28-set-1990|
|Appare nelle tipologie:||01 - Articolo su periodico|