Direct activation of phospholipase C-gamma by fibroblast growth factor receptor is not required for mesoderm induction in Xenopus animal caps.
Members of the fibroblast growth factor (FGF) family induce mesoderm formation in explants of Xenopus embryonic ectoderm (animal caps). Recent studies have been directed at determining signaling pathways downstream of the FGF receptor that are important in mesoderm induction. We have recently shown that a point mutation in the FGF receptor changing tyrosine 766 to phenylalanine (Y/F mutation) abolishes phospholipase C-gamma (PLC-gamma) activation in mammalian cells. To explore the role of PLC-gamma activation in FGF-stimulated mesoderm induction, we constructed two chimeric receptors, each consisting of the extracellular portion of the platelet-derived growth factor beta receptor, with one having the transmembrane and intracellular portions of the wild-type FGF receptor 1 (PR-FR wt) and the other having the corresponding region of the Y/F766 mutant FGF receptor 1 (PR-FR Y/F766). When expressed in Xenopus oocytes, only PR-FR wt was able to mediate PLC gamma phosphorylation, inositol-1,4,5-trisphosphate accumulation, and calcium efflux in response to platelet-derived growth factor stimulation. However, both receptors mediated mesoderm induction in Xenopus animal caps as measured by cap elongation, muscle-specific actin mRNA induction, and skeletal muscle formation. These results demonstrate that PLC gamma activation by the FGF receptor is not required for FGF-stimulated mesoderm induction.
Muslin
A J
AJ
Program of Excellence in Molecular Biology, University of California, San Francisco 94143-0130.
Peters
K G
KG
Williams
L T
LT
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004475:Ectoderm / Q000187:drug effects / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017354:Point Mutation; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000378:metabolism*; D014981:Xenopus
D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium