Interleukin 3-stimulated proliferation is sensitive to pertussis toxin: evidence for a guanyl nucleotide regulatory protein-mediated signal transduction mechanism.
Interleukin 3 (IL-3) stimulates several biochemical and biological responses in IL-3-dependent tissue culture cells. We examined the possibility that guanyl nucleotide regulatory (G) proteins may transduce signals from IL-3 receptors. We report here that pertussis toxin (PT), which can covalently modify a subclass of G proteins, is capable of inhibiting IL-3-stimulated proliferation in a dose-dependent fashion. PT inhibition of IL-3-stimulated proliferation could be overcome by using the Ca++ ionophore A23187 in conjunction with TPA. PT could also inhibit IL-3-stimulated hexose transport. In the absence of IL-3, hexose transport could be stimulated by introducing GTP-gamma S into intact cells. From these data we propose that IL-3 receptors transduce signals via a PT-sensitive G protein(s).
Kelvin
D J
DJ
Department of Anatomy, University of Toronto, Canada.
Shreeve
M
M
McAuley
C
C
McLeod
D L
DL
Simard
G
G
Connolly
J A
JA
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D037342:Pertussis Toxin; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D007377:Interleukin-3; D009004:Monosaccharide Transport Proteins; D010566:Virulence Factors, Bordetella; D000001:Calcimycin; D003994:Bucladesine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate