The proto-oncogene c-myb mediates an intracellular calcium rise during the late G1 phase of the cell cycle.
The intracellular concentration of ionized calcium is involved in regulating mitosis. However, little is known about intracellular levels of calcium during G1. We have demonstrated in vascular smooth muscle cells a mid-G1 decrease in ionized calcium concentration followed by a 2-fold rise at the G1/S interface (44 nM +/- 0.6 nM versus 98 nM +/- 1.1 nM, p < 0.01). The elevation of intracellular calcium is preceded by an increase in c-myb mRNA levels and is abolished with antisense but not missense c-myb oligonucleotides. Furthermore, cells stably transfected with c-myb show a similar 2-fold augmentation in intracellular calcium concentrations, as compared with untransfected cells, which is also abolished by antisense c-myb oligonucleotides. The c-myb-induced rise in intracellular calcium is dependent upon the presence of extracellular calcium and is not suppressed by L type calcium channel blockers. We conclude that c-myb induces an elevation in intracellular calcium levels of vascular smooth muscle cells at the G1/S interface which provides a novel role for this proto-oncogene as well as a potentially important control point for cell cycle regulation.
Simons
M
M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Morgan
K G
KG
Parker
C
C
Collins
E
E
Rosenberg
R D
RD
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics; D005456:Fluorescent Dyes; D016257:Fura-2; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D007211:Indoles; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009857:Oncogenes; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D012091:Repetitive Sequences, Nucleic Acid; D014162:Transfection
D003470:Culture Media; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D007211:Indoles; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; C048960:indo-1; D002118:Calcium; D016257:Fura-2