12-O-Tetradecanoylphorbol-13-acetate-induced dephosphorylation of protein kinase Cα correlates with the presence of a membraneassociated protein phosphatase 2A heterotrimer

Abstract

Protein kinase C signaling is desensitized through a combination of dephosphorylation and proteolysis in intact cells. The process of dephosphorylation is analyzed here, as well as its relationship to degradation. It is established for protein kinase Cα that dephosphorylation occurs in a membrane compartment following activation and temporally preceding significant degradation. The phosphatase responsible for the dephosphorylation appears to be a heterotrimeric type 2A phosphatase, which is shown to be in part constitutively membrane associated. Consistent with a role for this activity, okadaic acid is shown to inhibit the phorbol ester-induced dephosphorylation of protein kinase C that occurs in intact cells. Furthermore, phorbol ester-induced down-regulation of protein kinase Ca is shown not to be dependent on the rate of dephosphorylation, indicating that these desensitizing pathways may operate in parallel.