Signalling pathways involved in cell-scattering: The role of protein kinase C (Hungarian text)

We have demonstrated that protein kinase C (PKC) plays antagonistic regulatory roles in the scattering of HepG2 cells induced by hepatocyte growth factor (HGF)/scatter factor or phorbol ester, Though the activity of PKC accounts for the phorbol ester-induced motility, the HGF-induced migration of HepG2 cells is decreased by PKC.; We have observed that phorbol ester-induced migration of HepG2 cells is accompanied by intensive actin stress fiber formation. The polymerisation of actin stimulated by phorbol ester-activated PKC is not prevented by the inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) indicating that PI 3-kinase is not involved in the initiation of this process. The phorbol ester-induced migration is not prevented by the inhibition of Src tyrosine kinase, either.; We have demonstrated that p21-activated protein kinase (PAK) is activated in phorbol ester treated cells, and this effect is also not prevented by the inhibition of PI 3-kinase or Src kinase. PAK 1 is transiently down regulated during the migration.; We have demonstrated that the migration of HepG2 cells is accompanied by enhanced ?2 and ?1 integrin expression. Phorbol ester-activated PKC enhances the integrin expression, while in HGF-induced cells PKC decreases the intensity of integrin expression. The activity of PI 3-kinase is essential for the growth factor-induced integrin expression.; We have demonstrated that the duration of PI 3-kinase activation in HGF-treated cells increases when PKC is inhibited. In the EGF signalling system PKC has no similar effect on PI 3-kinase. Our observations suggest that the molecular background of the negative modulatory effect of PKC on the HGF-induced migration is the termination of PI kinase activation. Phorbol ester-activated PKC seems to be able to stimulate the migration of HepG2 cells via another signalling route, which does not require the activity of PI 3-kinase.