The role of protein kinase in human synovial fibroblast growth.
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.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Tsukada
T
T
Kawabe
Y
Y
Aoyagi
T
T
Nagataki
S
S
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
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