In testing the hypothesis that the stimulation of the release of fibronectin (FN) by 12-O-tetradecanoylphorbol 13-acetate (TPA) from human lung fibroblasts in culture is the result of activation of protein kinase C (PKC), we found that the PKC inhibitor sphingosine strongly inhibited FN release in presence and even in absence of TPA. However, a different PKC inhibitor, calphostin C, despite almost complete inhibition of PKC, had no effect on FN release. We concluded that sphingosine is a potent inhibitor of FN release from the cell surface, independent of its inhibition of PKC; and that TPA stimulates release of FN by a pathway other than activation of PKC. We found that the activation of PKC by TPA was accompanied by inhibition of the cAMP-dependent protein kinase (PKA). When PKA was inhibited by an antagonist (H8, a cAMP analogue) at a concentration specific for PKA inhibition, the release of FN was stimulated similar to the stimulation with TPA. Activation of PKA with forskolin resulted in decreased FN release. In conclusion, we have shown that: (1) sphingosine had a robust effect inhibiting the release of FN from fibroblasts, independent of its action on PKC; (2) TPA treatment of these cells resulted in inhibition of PKA; (3) inhibition of PKA stimulated FN release whereas its activation decreased this release. It is possible that PKA, by phosphorylating a protein, may function, directly or indirectly, in keeping FN attached to the cell surface of fibroblasts.
The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture / H. Scheidl, G. Scita, P. H. Sampson, H. Y. Park, G. Wolf. - In: BIOCHIMICA ET BIOPHYSICA ACTA. - ISSN 0006-3002. - 1135:3(1992 Jun 29), pp. 295-300-300.
|Titolo:||The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture|
SCITA, GIORGIO (Secondo)
|Parole Chiave:||(Fibroblast); 12-O-tetradecanoylphorbol 13-acetate; Calphostin C; Fibronectin; Phorbol ester; Protein kinase C; Sphingosine; Tumor promoter|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||29-giu-1992|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0167-4889(92)90234-3|
|Appare nelle tipologie:||01 - Articolo su periodico|