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Protein kinase C levels and protein phosphorylation associated with inhibition of proliferation in a murine macrophage tumor
Author(s) -
Goode Nigel T.,
Hart Ian R.
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041420306
Subject(s) - protein kinase c , phorbol , cell growth , phosphorylation , phorbol ester , tetradecanoylphorbol acetate , cell culture , protein kinase a , microbiology and biotechnology , kinase , biology , biochemistry , chemistry , genetics
Abstract Treatment of M5076 tumor cells with the phorbol esters 12‐O‐tetradecanoyl‐phorbol 13‐acetate (TPA) and phorbol 12, 13 dibutyrate (PdBu) inhibited cellular proliferation, whereas 1,2‐dioctanoyl‐glycerol (DiC8) and 1‐oleoyl2‐acetyl‐glycerol (OAG) did not affect cell growth. Inhibition of cellular proliferation in this cell line appears to be a consequence of protein kinase C (PKC) down‐regulation since phorbol esters, but not a single application of diacylglycerols (DGs) down‐regulated cellular PKC levels. By repeated application of DGs, PKC down‐regulation was achieved and correlated with inhibition of proliferation. Phorbol ester‐induced PKC down‐regulation was reversible, upon removal of the phorbol ester, and the reappearance of PKC was associated with resumption of proliferation. The mitogenic responsiveness of these cells to added serum depended upon cellular PKC levels. Phorbol esters also caused the phosphorylation of two proteins which were not phosphorylated in response to DG treatment. Inhibition of growth of M5076 cells appears to be associated with phosphorylation of two novel proteins and/or PKC down‐regulation.