Growth factor starvation of bcl-2 overexpressing murine bone marrow cells induced refractoriness to IL-3 stimulation of proliferation.
Murine bone-marrow derived BAF3 cells, over-expressing the human Bcl-2 gene product, showed considerably delayed onset of apoptosis when deprived of IL-3. Such Bcl-2-BAF3 cells arrested rapidly in the G1 phase of the cell cycle upon IL-3 removal, then became refractory to IL-3 re-stimulation. The delay in IL-3 induced proliferation of Bcl-2 over-expressing cells was due to down-regulation of a specific signalling pathway. In the refractory cells, IL-3 was able to stimulate protein tyrosine phosphorylation and c-myc mRNA accumulation, but not rapid Erk2 activation or cdc2 mRNA accumulation.
Marvel
J
J
Chester Beatty Laboratories, Institute of Cancer Research, London.
Perkins
G R
GR
Lopez Rivas
A
A
Collins
M K
MK
D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016193:G1 Phase; D007377:Interleukin-3 / Q000172:deficiency*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D011994:Recombinant Proteins
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D019950:Mitogen-Activated Protein Kinase 1