Protein kinase C activation increases binding of transcription factor PU.1in murine tissue macrophages

PU.1 is a transcription factor found in macrophages, B cells, neutrophils, and hemopoietic stem cells, In macrophages PU.1 regulates a number of genes , including c-fms, CD11b, CD18, and Fc gamma R1b, Previously, in primary ma crophages PU.1 binding to the sequence GAGGAA was found to be induced by tr eatment with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-g amma). Here we investigated the role of protein kinase C (pKC) in the induc tion of PU.1 binding in macrophages, We report that pharmacological activat ion of pKC increases PU.1 binding, while inactivation of pKC inhibits the i ncreases in PU.1 binding by agents which activate pKC in macrophages (LPS a nd tumor necrosis factor-alpha), but not by an agent which does not activat e pKC (IFN-gamma). pKC activation may therefore be one pathway by which PU. 1 binding may be increased in primary macrophages. (C) 1999 Academic Press.