Continuous synthesis of two protein-kinase-C-related proteins after down-regulation by phorbol esters.
The phorbol 12-myristate 13-acetate (PMA)-dependent down-regulation of immunoprecipitable protein kinase C was studied in human breast cancer cell lines that display different growth inhibitions toward the tumor promoter. PMA induces translocation of [35S]methionine-prelabeled cytosolic protein kinase C to membranes, followed by complete degradation of the enzyme (t1/2, 2 hr). PMA does not affect the protein kinase C synthesis; 20-80% of total protein kinase C of control cells was still immunoprecipitable as membrane-bound 74- and 80-kDa protein kinase C-related polypeptides if cells were allowed to incorporate [35S]methionine during PMA exposure for greater than 6 hr. These two proteins lack protein kinase activity and phorbol ester binding but reveal V8 peptide patterns identical to the active forms of protein kinase C (77/80 kDa) of PMA-untreated cells. The amounts of the immunoprecipitable membrane-bound 80-kDa protein kinase C-related polypeptide synthesized during the prolonged PMA treatment appear to inversely correlate with the extent of PMA-mediated growth inhibition of the respective human breast cancer cell line. These data suggest that after homologous down-regulation, functional protein kinase C (77/80 kDa) is replaced by a population of membrane-associated but enzymatically inactive protein kinase C-related polypeptides (74/80 kDa).
Borner
C
C
Department of Research, University Clinic Medical School, Basel, Switzerland.
Eppenberger
U
U
Wyss
R
R
Fabbro
D
D
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D003864:Depression, Chemical; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000201:enzymology
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate