IL-3 stimulated haemopoietic stem cell proliferation: evidence for G protein independent mitogenic signalling events.
Interleukin-3 stimulates the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. We have investigated the possible involvement of a guanyl nucleotide regulatory (G) protein(s) in the IL-3 stimulated proliferative response. We report here that pertussis toxin (PT) can partially inhibit IL-3 stimulated DNA synthesis and that this inhibition is bypassed by TPA. The ADP-ribosylation of the PT substrate G protein in vivo is complete in 2 hours without concomitant inhibition of IL-3 stimulated hexose transport or Na+/H+ exchange. When loaded into FDCP-Mix 1 cells fluoroaluminate and GTP-gamma-S, which can directly activate G proteins, are not capable of mimicking the effects of IL-3. Evidence is also presented that IL-3 does not stimulate a membrane-bound high affinity GTPase activity in the FDCP-Mix 1 cell line. These data suggest that a PT substrate G protein(s) can influence the IL-3 signalling cascade in an indirect or permissive manner, but that the IL-3 receptor does not directly couple to a PT substrate G protein.
Akinsanya
A A
AA
Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom.
Whetton
A D
AD
D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004247:DNA / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D008934:Mitogens / Q000502:physiology*; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D006601:Hexoses; D007377:Interleukin-3; D008934:Mitogens; D017923:Sodium-Hydrogen Exchangers; D004247:DNA; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins