The role of MAP kinase kinase in interleukin-3 stimulation of proliferation.
Expression of a dominant interfering mutant of MAP kinase kinase (MAPKK) inhibits interleukin-3 (IL-3) activation of MAP kinase in the murine bone marrow-derived cell line BAF3. This results in an increase in the level of IL-3 required to stimulate cell proliferation and suppress apoptosis. When apoptosis is constitutively inhibited by coexpression of bcl-2, the dominant interfering MAPKK inhibits IL-3 driven cell cycle progression. Thus, MAPKK function is necessary for optimal IL-3 inhibition of apoptosis and optimal IL-3 stimulation of entry into S phase. Expression of a constitutively activated mutant of MAPKK does not replace IL-3, but renders cells able to proliferate in a density-dependent manner. Cell contact is required to allow cell proliferation; such contact can be supplied by cells without activated MAPKK.
Perkins
G R
GR
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, London, UK.
Marshall
C J
CJ
Collins
M K
MK
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D005799:Genes, Dominant; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D011494:Protein Kinases / Q000502:physiology*
D007377:Interleukin-3; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases