Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK)-independent functions of Raf kinases

Raf comprises a family of three kinases, A-Raf, B-Raf and Raf-1, which are best known as key regulators of the MEK—MAPK/ERK cascade. This module is often perceived as a linear pathway in which ERK is the effector. However,recent advances have unveiled a role for Raf outside this established signalling unit. Current evidence, including gene-knockout studies in mice,suggests that there are ERK-independent functions of Raf kinases. Regulation of apoptosis is one area in which Raf may function independently of ERK,although its substrates remain to be identified. Other studies have suggested that Raf has kinase-independent functions and may act as a scaffold protein.