A-Raf: Proteins and Enzymes

The Raf serine/threonine kinases are effectors of Ras that function as MAP3Ks in the ERK phosphorylation cascade. Mammals express three Raf proteins: A-Raf, B-Raf, and Raf-1, also known as C-Raf. Human A-Raf is a 70 kDa protein that shares three regions with B-Raf and Raf-1: aa 14-153 which contains a Ras-binding domain, a Cys-rich domain, and a lipid-binding domain; aa 209-223; and aa 308-573 which contains the Ser/Thr protein kinase domain and a second lipid-binding domain. A-Raf is activated by phosphorylation at Ser 257, 262, and 264. It then regulates multiple processes including endocytic trafficking, glycolysis, cell cycle progression, and apoptosis.