Ras is a mediator of TGFbeta1 signaling in developing chick ciliary ganglion neurons.
Large-conductance Ca(2+)-activated K(+) channels (K(Ca)) in chick ciliary ganglion neurons are regulated by target-derived TGFbeta1. Here we show that TGFbeta1 stimulation of K(Ca) expression was blocked by the structurally dissimilar Ras protein farnesyl transferase inhibitors manumycin-A and FTI-277. A similar effect was produced in ciliary neurons overexpressing RasN17, a widely used dominant-negative form of Ras. Moreover, TGFbeta1-evoked increases in phosphorylation of SMAD2 were reduced by manumycin-A, suggesting that Ras-dependent transduction cascades activated by TGFbeta1 feed back onto SMAD signaling. Thus, Ras is a mediator of pleiotropic TGFbeta1 signaling in developing neurons.
Lhuillier
Loic
L
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.
Dryer
Stuart E
SE
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000196:embryology*; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D018631:ras Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C096856:FTI 277; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D024681:Potassium Channels, Calcium-Activated; D051899:Smad2 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D018631:ras Proteins; C054474:manumycin