Role of calmodulin-dependent phosphorylation of elongation factor 2 in the proliferation of rat glial cells.

Abstract

Calmodulin (CaM) is believed to play an important role in the regulation of cellular proliferation. The mechanism of regulation, although unknown, may involve CaM-binding proteins, particularly CaM-dependent protein kinases. Previously, we have shown that CaM-dependent protein kinase III phosphorylates elongation factor 2 (EF-2) in proliferating, C6 glioma cells but not in normal white matter, a tissue rich in nonproliferating glia. To determine whether CaM-dependent phosphorylation of EF-2 is linked, in general, to cellular division, we studied the phosphorylation of EF-2 in proliferating and growth-arrested C6 cells and in proliferating, primary cultures of normal glia. Phosphorylation of EF-2 was not detectable in C6 cells arrested in their growth by serum deprivation. When serum-deprived cells were stimulated to proliferate by the re-addition of serum, the amount of phosphorylated EF-2 correlated with levels of [3H]thymidine incorporation into DNA. Primary cultures of dividing, normal glia, obtained from neonatal rats, also demonstrated phosphorylation of EF-2. Therefore, the CaM-dependent phosphorylation of EF-2 appears to be associated with cellular proliferation in normal and malignant glia in the rat.