Dissociation of PDGF receptor tyrosine kinase activity from PDGF-mediated inhibition of gap junctional communication.
J Cell Physiol
; 158(3): 427-34, 1994 Mar.
Article
em En
| MEDLINE
| ID: mdl-8126067
ABSTRACT
Gap junction-mediated intercellular communication (GJC) may play an important role in cell proliferation and transformation since GJC is inhibited by growth factors, oncogenes, tumor promoters, and carcinogens. We have studied inhibition of GJC by platelet-derived growth factor-BB (PDGF) in the mouse fibroblast cell line C3H/10T1/2 and have sought to determine whether PDGF-induced inhibition of GJC is mediated by the PDGF receptor tyrosine kinase (RTK). PDGF-mediated inhibition of GJC was rapid and transient, with maximal inhibition occurring 40 min after PDGF addition and GJC returning to control levels after 70 min. The effect of PDGF on GJC was concentration-dependent, with maximal inhibition of 90% or greater occurring at 10 ng/ml PDGF. Stimulation of RTK activity, as determined by antiphosphotyrosine immunoblot analysis of PDGF receptor and the receptor substrates phospholipase C-gamma I (PLC-gamma I) and guanosine triphosphatase activating protein (GAP), was also concentration-dependent. Inhibition of GJC required a greater concentration of PDGF than did stimulation of RTK activity. The tyrosine kinase inhibitor genistein blocked PDGF-induced RTK activity, as measured by PDGF receptor, PLC-gamma I, and GAP tyrosine phosphorylation, in a concentration-dependent manner but did not affect PDGF-mediated inhibition of GJC. Genistein alone had no effect on GJC or PDGF receptor expression. PDGF treatment in the presence or absence of genistein resulted in phosphorylation of the connexin 43 protein on nontyrosine residues. These results suggest that inhibition of GJC by ligand-activated PDGF receptor is dissociable from the RTK activity responsible for PDGF, PLC-gamma I, and GAP phosphorylation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Fator de Crescimento Derivado de Plaquetas
/
Receptores do Fator de Crescimento Derivado de Plaquetas
/
Junções Comunicantes
/
Fibroblastos
Limite:
Animals
Idioma:
En
Ano de publicação:
1994
Tipo de documento:
Article