Role of calmodulin-dependent phosphorylation of elongation factor 2 in the proliferation of rat glial cells.
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.
Bagaglio
D M
DM
Department of Pharmacology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5638.
Hait
W N
WN
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D054736:Elongation Factor 2 Kinase; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005910:Glioma; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D005904:Glial Fibrillary Acidic Protein; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D004533:Egtazic Acid; C517691:Eef2k protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054736:Elongation Factor 2 Kinase; D002118:Calcium; D013936:Thymidine