Using murine myeloid factor-dependent FDC-P1/ER cells, we demonstrate that the hematopoietic growth factors interleukin-3 and erythropoietin and bryostatin-1, a macrocyclic lactone natural product and potent activator of protein kinase C (PKC), suppress apoptosis and induce the rapid serine phosphorylation of Bcl2α. Expression of recombinant wild type Bcl2α in NFS/N1·H-7 cells confirms that murine Bcl2α is phosphorylated following PKC activation. The PKC inhibitors H-7 and staurosporine, but not the protein kinase A inhibitor HA1004, block not only interleukin-3- and bryostatin-1- induced hyperphosphorylation of Bcl2α but also their anti-apoptotic effect on growth factor-dependent cells, suggesting a role for activated PKC in both processes. A potential direct role for a classic isoform of PKC is indicated by the Ca2+-dependent nature of phosphorylation of Bcl2α mediated by purified PKC in vitro. Comparative phosphopeptide maps confirm that Bcl2α phosphorylation occurs on identical serine site(s) whether phosphorylation occurs in cells following agonist treatment or directly by PKC in vitro. These findings strongly support a role for activated PKC in growth factor- induced Bcl2α phosphorylation as well as suppression of apoptosis.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - Oct 28 1994|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology