The identification of two novel ligands of the FGF receptor by a yeast screening method and their activity in Xenopus development.
We have developed a functional screen in yeast to identify ligands for receptor tyrosine kinases. Using this method, we cloned two Xenopus genes that activate the fibroblast growth factor (FGF) receptor. These encode novel secreted proteins, designated FRL1 and FRL2, distantly related to the epidermal growth factor and angiogenin/ribonuclease families, respectively. Both genes activate the FGF receptor in Xenopus oocytes as well as in yeast. Overexpression induces mesoderm and neural-specific genes in Xenopus explants; induction is blocked by a dominant negative inhibitor of the FGF receptor. FRL1 is broadly expressed during gastrulation and neurulation, while FRL2 is expressed principally in the axial mesoderm and brain at later stages. Our results indicate that despite their lack of similarity with FGF, FRL1 and FRL2 are ligands for the FGF receptor that play distinct roles in development.
Kinoshita
N
N
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Minshull
J
J
Kirschner
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004627:Embryonic Induction / Q000235:genetics; D015723:Gene Library; D005820:Genetic Testing; D015151:Immunoblotting; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013997:Time Factors; D014170:Transformation, Genetic; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
D018076:DNA, Complementary; D008024:Ligands; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; C096789:loc100496462 protein, Xenopus; C096788:tdgf1.3 protein, Xenopus