Intracellular signal transduction for serum activation of the hyaluronan synthase in eukaryotic cell lines.
Hyaluronan synthase was activated in B6 cells or 3T3 fibroblasts by foetal calf serum with maximal activity after 6 h. Activation was inhibited by cycloheximide or by the protein kinase inhibitors H-7 or H-8, indicating that transcription as well as phosphorylation was required for activation. The activation by serum was markedly prolonged, when serum was added together with cholera toxin or theophylline. Without serum stimulation the hyaluronan synthase could also be activated by phorbol-12-myristate-13-acetate, by dibutyryl-c-AMP, or by forskolin. Increasing the intracellular Ca-ion concentration with a Ca-ionophore also led to an activation. The activation of the drugs was not synergistic. In isolated plasma membranes the synthase activity could be decreased by phosphatase treatment and enhanced by ATP in B6 cells and by ATP in the presence of phorbol-12-myristate-13-acetate in 3T3 fibroblasts. Stimulation correlated with increased transcription and phosphorylation of the 52 kD hyaluronan synthase at serine residues. The results led to the conclusion that hyaluronan synthase is induced by transcription and activated by phosphorylation by protein kinase C, c-AMP-dependent protein kinases, or Ca-ion-dependent protein kinases.
Klewes
L
L
Institut für Physiologische Chemie und Pathobiochemie, Münster, Germany.
Prehm
P
P
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001790:Blood Physiological Phenomena; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004790:Enzyme Induction; D005057:Eukaryotic Cells / Q000201:enzymology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D016695:Glycosyltransferases; D000076002:Hyaluronan Synthases; D007425:Intracellular Membranes / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D014166:Transferases; D029867:Xenopus Proteins
D000596:Amino Acids; D008565:Membrane Proteins; D029867:Xenopus Proteins; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium