Isotype-specific functions of Raf kinases

The family of Raf-protein kinases consisting of A-Raf, B-Raf, and c-Raf-1 i s involved in cellular processes which regulate proliferation, differentiat ion, and apoptosis. Cell-culture experiments and the knockout of individual Raf genes suggested that the three Raf isoforms have overlapping and uniqu e regulatory functions. However, it is not known how these isotype-specific functions of Raf kinases occur in the cell. Published data suggest that Ra f proteins might differ in the regulation of their activation as well as in their ability to connect to downstream signaling pathways. Since Raf is pa rt of a multiprotein complex and protein-protein interactions are important for Raf signaling, we propose that isotype-specific functions can be achie ved by isotype-restricted protein binding. Recently we were able to identif y candidates for such Raf-isoform-specific interaction partners.