RESUMO
A complementary DNA clone corresponding to a 4.2-kilobase transcript that is present in the Xenopus oocyte and newly transcribed in the neurula stages of development has been isolated. This messenger RNA encodes a 155-amino acid protein that is 84% identical to the human basic fibroblast growth factor (bFGF). When expressed in Escherichia coli and purified, the Xenopus FGF induced mesoderm in animal cell blastomeres as measured by muscle actin expression. Immunoblots with an antibody to a Xenopus FGF peptide show that the oocyte and early embryo contain a store of the FGF polypeptide at high enough concentrations to induce mesoderm. The presence of FGF in the oocyte, together with the apparent lack of a secretory signal sequence in the protein, suggest that the regulation of mesoderm induction may involve novel mechanisms that occur after the translation of FGF.
Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , Mesoderma/citologia , Xenopus laevis/embriologia , Actinas/genética , Sequência de Aminoácidos , Animais , Northern Blotting , Western Blotting , Clonagem Molecular , DNA/genética , Sondas de DNA , Regulação da Expressão Gênica , Dados de Sequência Molecular , Oócitos/fisiologiaRESUMO
Vascular endothelial growth factor (VEGF) is a potent and selective mitogen for endothelial cells that is angiogenic in vivo and induced by hypoxia. A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture. The rat GS-9L glioma cell line produces not only VEGF homodimers but also PlGF homodimers and a novel heterodimer composed of VEGF and PlGF subunits. All three dimeric forms were purified to apparent homogeneity, and their structures and mitogenic activities were compared. VEGF.PlGF heterodimers are vascular endothelial cell mitogens nearly as potent as VEGF homodimers. Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF.PlGF heterodimers. In contrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious. However, the existence of not only homodimers but also heterodimers clearly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.
Assuntos
Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/isolamento & purificação , Linfocinas/biossíntese , Linfocinas/isolamento & purificação , Proteínas da Gravidez/biossíntese , Proteínas da Gravidez/isolamento & purificação , Sequência de Aminoácidos , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Cromatografia por Troca Iônica , Clonagem Molecular , Meios de Cultivo Condicionados , Eletroforese em Gel de Poliacrilamida , Fatores de Crescimento Endotelial/farmacologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Glioma , Substâncias de Crescimento/biossíntese , Substâncias de Crescimento/isolamento & purificação , Humanos , Linfocinas/farmacologia , Substâncias Macromoleculares , Dados de Sequência Molecular , Peso Molecular , Placenta , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/farmacologia , Multimerização Proteica , Ratos , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas , Veias Umbilicais , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Glioma-derived vascular endothelial cell growth factor (GD-VEGF) is a 46-kDa dimeric glycoprotein mitogen with apparently greater specificity for vascular endothelial cells than the well-characterized fibroblast growth factors. The GD-VEGF cDNA sequence encodes a 190-amino acid residue subunit that is converted, by removal of an amino-terminal hydrophobic secretory leader sequence, to the mature 164-residue subunit characterized by direct amino acid sequencing. The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains and its oncogene homologue v-sis.