Overview:

The Ras pathway is a critical signal transduction cascade that regulates cellular proliferation, differentiation, survival, and oncogenic transformation. The Ras family of membrane associated GTPases directly binds RAF1, its direct downstream effector (1). Activated RAF1 phosphorylates the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate the downstream serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration (2). Downregulation of RAF1 is regulated by phosphorylation at Ser301 and Ser642 (3).

References:

1. Rapp, U. et al: Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc. Nat. Acad. Sci. 80: 4218-4222, 1983.

2. Li, P. et al: Raf-1: a kinase currently without a cause but not lacking in effects. Cell 64: 479-482, 1991.

3. Dougherty M.K. et al: Regulation of Raf-1 by Direct Feedback Phosphorylation. Mol Cell 17:215-224, 2005.