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Phorbol esters inhibit the synthesis of acetylcholine receptors in cultured muscle cells
Author(s) -
Bursztajn Sherry,
Schneider Larry W.,
Jong YuhJin,
Berman Stephen A.
Publication year - 1988
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/j.1768-322x.1988.tb00741.x
Subject(s) - protein kinase c , biology , acetylcholine receptor , intracellular , extracellular , phorbol , acetylcholine , biochemistry , receptor , microbiology and biotechnology , kinase , endocrinology
The acetylcholine receptor (AChR) synthesis, insertion and degradation rates are regulated by numerous intracellular and extracellular agents. Recent studies have shown that Ca 2+ and Ca 2+ ionophores have a profound regulatory effect on the appearance of AChR clusters and AChR synthesis [3, 15, 23]. These regulatory effects may be mediated through the activation of calcium and phospholipid‐dependent protein kinases by agents such as phorbol esters. In this study, we have utilized 4‐β‐phorbol‐12‐myristate‐13‐acetate (PMA) in order to determine whether the activation of protein kinase C exerts a regulatory effect on the expression of AChRs in cultured chick myotubes. Our results show that 4‐β‐phorbol‐12‐myristate‐13‐acetate decreased intracellular AChRs and suppressed AChR synthesis without affecting the turnover rate. Control and PMA treated cells labeled with [ 35 S] methionine and immunoprecipitated with a monoclonal antibody to the α subunit of AChRs (mAb35) revealed a significant decrease in radioactivity precipitated after exposure to PMA. Polyacrylamide gel electrophoresis revealed no major changes in protein patterns, or in newly synthesized proteins as determined by [ 35 S] methionine incorporation and autoradiography. Other enzymes important in muscle metabolism were not affected by PMA treatment. Our results indicate that activation of protein kinase C results in the suppression of AChRs synthesis and dispersal of AChR clusters.