Protein kinase C activates chloride conductance in C127 cells stably expressing the cystic fibrosis gene.

The regulatory domain (R domain) of the cystic fibrosis transmembrane conductance regulator (CFTR) is phosphorylated by protein kinase A and protein kinase C (PKC) in vivo (Picciotto, M. R., Cohn, J. A., Bertuzzi, G., Greengard, P., and Nairn, A. C. (1992) J. Biol. Chem. 267, 12742-12752), but so far the functional effect of the PKC-dependent phosphorylation has not been clarified. We investigated the effect of PKC on the CFTR-mediated Cl- transport by treating with phorbol 12-myristate 13-acetate (PMA), the cell line C127i stably expressing CFTR wild type (C127 CFTRw/t), or CFTR bearing the most common mutation deltaF508 (C127 CFTRdF508). We show that PMA activates Cl- efflux in C127 CFTRw/t, but not in C127 CFTRdF508 and C127i. The PMA-dependent activation of CFTR is not mediated by increase of intracellular [cAMP] and is not the result of a primary activation of a K+ conductive pathway. These results strongly suggest that PKC activates directly CFTR-mediated Cl- transport.