Anti-A-Raf (N-terminal region) Antibody

The Ras-Raf-MAP kinase signaling pathway is involved in control of cell proliferation and differentiation. The Raf kinase family includes A-Raf, B-Raf, and C-Raf. Each family member has three highly conserved regions (CR1-3). The N-terminal CR1 contains the Ras-GTP-binding domain. The CR2 contains a negative regulatory serine residue (C-Raf (S259)/B-Raf(S365)) that may bind 14-3-3 proteins. The CR3 is the catalytic domain that contains phosphorylation sites for Raf-regulating enzymes within two segments, the N-region and the activation segment. Activation of C-Raf involves phosphorylation at many sites including Ser-338, Tyr-341, and Ser-471. The latter site is phosphorylated after EGF stimulation and may be important for MEK interaction in both C-Raf and A-Raf. In B-Raf, multiple phosphorylation sites have been identified, but their specific roles are uncertain. Phosphorylation of Ser-446 may prime B-Raf for activation, and Ser-446 and/or Ser-447 phosphorylation may be critical for B-Raf biological activity during PC12 differentiation. Ser-579 is required for growth factor activation and kinase activity.