ARAF
KSR1 (kinase suppressor of Ras 1) is a pseudokinase that acts as a molecular scaffold for the RAF-MEK-ERK cascade rather than as a catalyst. Although it retains a kinase-like fold, substitutions within conserved catalytic motifs render it catalytically inactive, so its role is to nucleate signaling complexes. KSR1 binds MEK constitutively through its pseudokinase domain and engages RAF and 14-3-3 proteins, positioning RAF next to its substrate to promote ERK activation downstream of Ras. A cysteine-rich CA1 domain mediates membrane recruitment after growth-factor stimulation. KSR1 is broadly expressed, with high levels in intestine and spleen, and modulates Ras-driven proliferation in development and oncogenic signaling.
