The nuclear location of annexin V in the human osteosarcoma cell line MG-63 depends on serum factors and tyrosine kinase signaling pathways.
Serum starvation of MG-63 cells increases their doubling time from 24 h to 4 days. Cells grown in medium containing 10% fetal calf serum contain high levels of annexin V in the cell nucleus, whereas growth for 4 days in the absence of serum results in loss of nuclear annexin V from 72 +/- 4% of cells. Many of the cells which still have nuclear annexin V under these conditions seem to have recently finished dividing. Refeeding cells with medium containing serum restores annexin V to nuclei within 5 h. Charcoal treatment removes factors from serum that are required to allow annexin V to return to the nucleus. Protein synthesis is not required for annexin V to return to nuclei since inhibition of protein synthesis with cycloheximide does not prevent the serum-induced return of annexin V to nuclei. This, and other evidence, indicates that the presence of annexin V in nuclei reflects translocation rather than catabolism and resynthesis. Inhibition of tyrosine kinase activities with genistein attenuates the relocation of annexin V from the cytoplasm to the nucleus. Thus, the nuclear location of annexin V is controlled by signaling pathways involving serum factors and tyrosine kinases. The results argue for an important role for annexin V in the cell nucleus.