Involvement of Protein Kinase Cε in the Negative Regulation of Akt Activation Stimulated by Granulocyte Colony-Stimulating Factor

摘要: Stimulation of cells with G-CSF activates multiple signaling cascades, including the serine/threonine kinase Akt pathway. We show in this study that G-CSF-induced activation myeloid 32D was specifically inhibited by treatment PMA, a protein C (PKC) activator. PMA also rapidly attenuated sustained mediated carboxy truncated receptor, expressed patients acute leukemia evolving from severe congenital neutropenia. The inhibitory effect abolished pretreatment specific PKC inhibitor GF109203X, suggesting pathway negatively regulates activation. Ro31-8820, PKCe inhibitor, abrogated PMA-mediated inhibition activation, whereas rottlerin and Go6976, inhibitors PKCδ PKCαβI, respectively, exhibited no significant effects. Furthermore, overexpression wild-type constitutively active, but not kinase-dead, forms markedly proliferation survival response to G-CSF. expression down-regulated terminal granulocytic differentiation. Together, these results implicate as negative regulator stimulated indicate plays role cell