Characterization of the molecular mechanism involved in the activation of hyaluronan synthetase by platelet-derived growth factor in human mesothelial cells.
The molecular mechanism involved in the stimulation of hyaluronan synthetase in normal human mesothelial cells was investigated. Exposure of mesothelial cells to platelet-derived growth factor (PDGF)-BB stimulated hyaluronan synthetase activity, measured in isolated membrane preparations, as well as hyaluronan secretion into the medium. The effect on hyaluronan synthetase was maximal after 6 h of treatment. In contrast, the stimulatory effect of transforming growth factor-beta 1 reached a maximum after 24 h. The stimulatory effect of PDGF-BB was inhibited by cycloheximide. The phosphotyrosine phosphatase inhibitor vanadate was found to stimulate hyaluronan synthetase activity, and to potentiate the effect of PDGF-BB. The protein kinase C (PKC) stimulator phorbol 12-myristate 13-acetate (PMA) also stimulated hyaluronan synthetase; furthermore, depletion of PKC by preincubation of the cells with PMA led to an inhibition of the PDGF-BB-induced stimulation of hyaluronan synthetase activity. Thus the PDGF-BB-induced stimulation of hyaluronan synthetase activity is dependent on protein synthesis and involves tyrosine phosphorylation and activation of PKC.
Heldin
P
P
Department of Medical and Physiological Chemistry, Biomedical Center, Uppsala, Sweden.
Asplund
T
T
Ytterberg
D
D
Thelin
S
S
Laurent
T C
TC
D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D007700:Kinetics; D008565:Membrane Proteins; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism; D014166:Transferases; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D029867:Xenopus Proteins
D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D013912:Threonine; D014638:Vanadates; D014443:Tyrosine; D012694:Serine; D003513:Cycloheximide; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate