Ca2+/calmodulin is involved in growth factor-induced retinoblastoma gene product phosphorylation in human vascular endothelial cells.
In human vascular endothelial cells, both growth factor-induced DNA synthesis and retinoblastoma gene product (RB) phosphorylation are absolutely dependent on extracellular Ca2+, and are potently inhibited by an active calmodulin antagonist, W-7, but not an inactive analogue, W-12. A reduction in the extracellular Ca2+ or an addition of W-7 as late as 8 h after growth factor stimulation still inhibits both RB phosphorylation and DNA synthesis to the full extent. However, once RB phosphorylation occurs 12-16 h after addition of the growth factors, it is not reversed by subsequent Ca2+ reduction or W-7. These results suggest the existence of a Ca2+/calmodulin-dependent process relatively late in the mitogenic signalling cascade, at a step proximal to RB phosphorylation reaction itself.
Takuwa
N
N
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Zhou
W
W
Kumada
M
M
Takuwa
Y
Y
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction
D002147:Calmodulin; D006133:Growth Substances; D016160:Retinoblastoma Protein; D002118:Calcium