Phorbol ester downregulates PDGFbeta receptor via PKCbeta1 in vascular smooth muscle cells.
The role of protein kinase C (PKC) and their isoforms in cell growth regulation remains elusive. Here we showed that in cultured human vascular smooth muscle cells (SMC), the PKC stimulator phorbol 12-myristate 13-acetate (PMA) inhibited [(3)H]thymidine incorporation in response to the growth factor PDGF associated with downregulation of PDGFbeta (but not alpha) receptors, which was recovered to normal level after PKC was depleted. The changes in PDGFbeta receptor were inversely correlated with PKCbeta1 protein levels regulated by PMA. The downregulation of PDGFbeta receptor by PMA was fully prevented by the PKCbeta inhibitor LY379196, however, without recovery of [(3)H]thymidine incorporation to PDGF. In contrast, [(3)H]thymidine incorporation was fully recovered after depletion of PKCs. These results indicate that in human SMC PKCbeta1 mediates PDGFbeta receptor downregulation. Other PKC isoforms activated by phorbol ester also contribute to the inhibitory effects on cell growth.
Yang
Z
Z
Vascular Biology, University of Fribourg, Fribourg, Switzerland. Zhihong.Yang@unifr.ch
Huerlimann
D A
DA
Viswambharan
H
H
Luescher
T F
TF
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D064546:Protein Kinase C beta; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007527:Isoenzymes; D020033:Protein Isoforms; D004247:DNA; D020797:Receptor, Platelet-Derived Growth Factor beta; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate