c-Raf is a mitogen-activated protein kinase. Binding of Raf to 14-3-3 is required for c-Raf kinase activity, and also blocks the ability of phosphatase to inhibit c-Raf. 14-3-3 binds c-Raf at two phospho-serine residues: Ser259 and Ser621. Mutation of Ser259 to alanine constitutively activates Raf kinase activity, but mutation of Ser621 to alanine results in an inactive kinase.