ACTIVATION OF MIL RAF PROTEIN-KINASES IN MITOTIC CELLS/

The c-Raf-1 protein kinase is a major element of several signal transd uction pathways and thought to be involved in entry into the S phase o f the cell cycle. Here we show that c-Raf-1 as well as the transformin g viral fusion protein Gag-Mil, in which most of the amino terminal re gulatory region of the avian Raf homologue Mil is deleted, are activat ed five- to sixfold in mitotic cells. Mitotic activation of Mil/Raf ki nase activity correlates with reduced electrophoretic mobility caused by hyperphosphorylation at serine/threonine residues located in the ca rboxy terminal part of c-Raf-1. Mitotic hyperphosphorylation occurs in various cell-lines indicating that it is ubiquitous. Our data suggest a novel function for Mil/Raf kinases in late stages of the cell cycle .