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Selective redistribution of protein kinase C isozymes by thapsigargin and staurosporine

1992; Oxford University Press; Volume: 13; Issue: 11 Linguagem: Inglês

10.1093/carcin/13.11.1997

1460-2180

Susan C. Kiley, Peter J. Parker, Doriano Fabbro, Susan Jaken,

Retinal Development and Disorders

Protein kinase C (PKC) is the major cellular receptor for tumor promoting phorbol esters. Phorbol esters activate α-, β-, δ- and є-PKCs in GH4C1 rat pituitary cells and cause their redistribution from a soluble to a particulate fraction. We have now characterized the effect of several non-phorbol ester tumor promoters on PKC isozyme distribution in GH4C1 cells. The incomplete tumor promoter mezerein caused redistribution of α-, β-, δ- and є-PKCs. Thus, it did not display partial agonist activity. The phosphatase inhibitor okadaic acid did not cause redistribution of any isozyme. The calcium ATPase inhibitor thapsigargin and the ser/thr kinase inhibitor staurosporine caused redistribution of є-PKC and, to a lesser extent, δ-PKC. Although the mechanism of the selective effect on δ- and є-PKCs is not yet known, these data clearly demonstrate that their subcellular distribution can be regulated by a pathway that does not influence α- and β-PKCs. Phorbol ester activation of є-PKC was associated with appearance of a more slowly migrating immunoreactive band in the paniculate fraction. Both є-PKC forms accumulated phosphate during phorbol ester treatment The phosphorytated forms of є-PKC were preferentially recovered in the particulate fraction. Although staurosporine caused redistribution, it prevented the phorbol dibutyrate (PDBu)-mediated appearance of the upper band of the doublet and the increased phosphorylation of both bands. The PDBu-mediated redistribution of α- and β-PKCs was not inhibited by staurosporine, even though staurosporine effectively inhibited PKC catalytic activity. Therefore, catalytic activity is not required for redistribution.