Ca2+-dependent cell surface protein phosphorylation may be involved in the initiation of DNA synthesis.
Incubating T51B rat liver cells in Ca2+-deficient, serum-rich medium containing only 0.02 mM Ca2+ strikingly decreased the phosphorylation of several trypsin-removable cell surface proteins and arrested the cells in late G1 phase. Raising the Ca2+ concentration in the Ca2+-deficient medium from 0.02 mM to 0.5 mM or adding 80 nM TPA (12-O-tetradecanoyl-phorbol-13-acetate), a protein kinase C activator, stimulated the phosphorylation of a certain set of surface proteins within 5 min and the initiation of DNA replication within the next 2 hr. By contrast, incubation in the same Ca2+-deficient medium, which does not affect the proliferation of neoplastic T51B-261B cells, did not reduce the phosphorylation of cell surface proteins. These observations suggest that the stimulation of a Ca2+-dependent protein kinase (possibly protein kinase C) directly or indirectly phosphorylates certain cell surface proteins that might be part of the mechanism that triggers the Ca2+-dependent G1----S transition of normal cells. They also suggest that an alteration of this Ca2+-dependent protein kinase might be the reason for neoplastic cells being able to proliferate in the face of an external Ca2+ shortage that would stop the proliferation of normal cells.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D008565:Membrane Proteins; D010750:Phosphoproteins; D000255:Adenosine Triphosphate; D004247:DNA; D011494:Protein Kinases; D014357:Trypsin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium