The pim-1 oncogene is regulated by hematopoietic cytokine receptors, e
ncodes a serine/threonine protein kinase, and cooperates with c-myc in
lymphoid cell transformation. Using a yeast two-hybrid screen, we fou
nd that pim-1 protein binds to p100, a transcriptional coactivator tha
t interacts with the c-Myb transcription factor. Pim-1 phosphorylated
p100 in vitro, formed a stable complex with p100 in animal cells, and
functioned downstream of Ras to stimulate c-Myb transcriptional activi
ty in a p100-dependent manner. Thus, pim-1 and p100 appear to be compo
nents of a novel signal transduction pathway affecting c-Myb activity,
linking all three to the cytokine-regulated control of hematopoietic
cell growth, differentiation, and apoptosis.