title: The role of protein kinase in human synovial fibroblast growth.
abstract: The histological features of rheumatoid arthritis (RA) consist of overgrowth of synovial cells. Several growth factors that cause synovial hyperplasia have been identified in RA synovium. The basic-fibroblast growth factor (b-FGF), representing one of these growth factors, may play an important role in the pathogenesis of RA. We examined the b-FGF-mediated intracellular signal pathway involved in synovial cell growth. b-FGF-induced synovial cell growth was inhibited by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, but not by H7 that inhibits protein kinase C (PKC). Stimulation of synovial cells with b-FGF resulted in tyrosine phosphorylation of cellular proteins and MAP kinase activation. Our results also demonstrated that b-FGF-mediated activation of MAP kinase was inhibited by herbimycin A indicating that protein tyrosine kinase may be involved in the activation of MAP kinase in human synovial cells. However, inhibition of b-FGF-mediated MAP kinase activation by PKC downregulation did not occur.
authors.affiliation: First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Tsukada
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: S
authors.initials: S
authors.lastname: Nagataki
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D016227:Benzoquinones; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology; D019833:Genistein; D006801:Humans; D006965:Hyperplasia; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D007529:Isoflavones; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D010879:Piperazines; D011809:Quinones; D016222:Fibroblast Growth Factor 2; D017828:Rifabutin; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013936:Thymidine