Intracellular signalling pathways involved in mesoderm induction by FGF.
We have examined the possible role of two signal transducing mechanisms, tyrosine phosphorylation and activation of protein kinase C (PKC), during fibroblast growth factor (FGF)-induced mesoderm induction in Xenopus. Tyrosine phosphorylation was examined through the use of a monoclonal anti-phosphotyrosine antibody. This antibody was shown to recognize the FGF receptor crosslinked to radioiodinated FGF. We also studied the response of Xenopus ectodermal explants to sodium orthovanadate, a compound that has been shown to elevate intracellular phosphotyrosine levels. Thirty percent of explants cultured in 100 microM vanadate were induced. In addition, vanadate synergized with FGF to give inductions that were more dorsal in nature than either vanadate or FGF alone. The role of PKC was evaluated by measuring PKC activity during mesoderm induction by FGF and by examining the effect of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on explants. TPA did not induce mesoderm, however, activation of PKC was detected in FGF-treated explants. Therefore, activation of the PKC pathway alone is not sufficient for mesoderm induction. Simultaneous treatment with TPA and FGF resulted in a significant inhibition of mesoderm induction by FGF, suggesting that activation of PKC could be part of a negative feedback mechanism. In contrast, TPA had no effect on induction by activin A.
Gillespie
L L
LL
Terry Fox Cancer Research Laboratories, Faculty of Medicine, Memorial University, St. John's, NF, Canada.
Paterno
G D
GD
Mahadevan
L C
LC
Slack
J M
JM
D028341:Activins; D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D004357:Drug Synergism; D004627:Embryonic Induction / Q000187:drug effects*; D005246:Feedback; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007265:Inhibins / Q000494:pharmacology; D008648:Mesoderm / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D014981:Xenopus / Q000196:embryology
D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D028341:Activins; D014638:Vanadates; D007265:Inhibins; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate