Activation of Mil/Raf protein kinases in mitotic cells.
The c-Raf-1 protein kinase is a major element of several signal transduction pathways and thought to be involved in entry into the S phase of the cell cycle. Here we show that c-Raf-1 as well as the transforming viral fusion protein Gag-Mil, in which most of the amino terminal regulatory region of the avian Raf homologue Mil is deleted, are activated five- to sixfold in mitotic cells. Mitotic activation of Mil/Raf kinase activity correlates with reduced electrophoretic mobility caused by hyperphosphorylation at serine/threonine residues located in the carboxy 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.
Lovrić
J
J
Institut fuer Medizinische Virologie, Universitaet Zuerich, Switzerland.
Moelling
K
K
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011784:Quail
D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D015739:Nocodazole