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.

Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence / T. Imamura, K. Engleka, X. Zhan, Y. Tokita, R. Forough, D. Roeder, A. Jackson, J. A. Maier, T. Hla, T. Maciag. - In: SCIENCE. - ISSN 0036-8075. - 249:4976(1990 Sep 28), pp. 1567-1570.

Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence

J.A. Maier;
1990

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.
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 MED/04 - Patologia Generale
28-set-1990
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/184600
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