Phorbol ester, prolactin, and relaxin cause translocation of protein kinase C from cytosol to membranes in human endometrial cells.
Incubation of endometrial cells with 100 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2, 5, 10 and 30 min decreased cytosolic protein kinase C (PKC) activity to 80%, 68%, 66%, and 72% of the control values, while membrane-associated PKC increased to 116%, 168%, 154% and 134% of the control values, respectively. Long-term incubation of cells with TPA resulted in a loss in total PKC activity. Treatment of secretory endometrial cells with prolactin (100 ng/ml) decreased cytosolic PKC to 64% (10 min) and 72% (20 min) while membrane PKC increased to 133% (10 min) and 158% (20 min) compared to control values. Relaxin (100 ng/ml) also caused translocation of PKC in secretory endometrium. Neither hormone induced PKC translocation in proliferative endometrium. In intact endometrial cells TPA stimulated the phosphorylation of an 80 kDa protein. Cytosolic protein phosphorylation in the presence of EGTA resulted in phosphorylation of proteins of 68 kDa and 19 kDa which was increased by prolactin. Upon activation by calcium and phosphatidylserine, PKC phosphorylated a protein of 39 kDa, and prolactin did not further enhance its phosphorylation. The present results indicate that TPA induces an intracellular translocation and down-regulation of PKC. The translocation of PKC by prolactin and relaxin suggests an involvement of this enzyme in the action of these hormones in human endometrium.
Kalbag
S S
SS
Department of Pathology, Nassau County Medical Center, East Meadow, NY 11554.
Roginsky
M S
MS
Jelveh
Z
Z
Sulimovici
S
S
D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012065:Relaxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D011388:Prolactin; D012065:Relaxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate