Evidence for a modulatory role of protein kinase C on glycosaminoglycan biosynthesis during the spontaneous differentiation of Caco-2 cells.
The role of protein kinase C (PKC) in the regulation of glycosaminoglycan (GAG) sulfation was investigated during the spontaneous differentiation of Caco-2 cells. The total cellular activity of PKC as well as its subcellular distribution was examined from d 5 (non-differentiated cells) to d 15 (enterocytic differentiated cells): during this period, PKC was redistributed from the membrane to the cytosol, but the amount of PKC activity was not modified. This redistribution of PKC was concomitant with an increase in 35S-sulfate incorporation in GAG. 4-beta phorbol 12 beta-myristate, 13-alpha acetate (PMA) and 1-2 dioctanoyl-glycerol (DIC8), 2 PKC activators, decreased 35S-sulfate incorporation in GAG; by contrast, 4 alpha-phorbol 12,13 didecanoate (4 alpha-PDD), an inactive phorbol ester, proved to be ineffective. These results suggest that membrane-bound PKC which is the active form of the enzyme, may exert on GAG sulfation a modulatory role, which is gradually attenuated as Caco-2 cell differentiation progresses.
INSERM, Faculté de Médecine Saint-Antoine, Laboratoire de Biochimie, Paris, France.
P
P
Lévy
G
G
Cherqui
A
A
Robert
D
D
Wicek
J
J
Picard
D001692:Biological Transport; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D003110:Colonic Neoplasms; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D006025:Glycosaminoglycans; D013431:Sulfates; C044295:1,2-dioctanoylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate