Isotype-specific functions of Raf kinases.

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