KSR STIMULATES RAF-1 ACTIVITY IN A KINASE-INDEPENDENT MANNER

Kinase suppressor of Ras (KSR) is an evolutionarily conserved componen t of Ras-dependent signaling pathways. Here, we find that murine KSR ( mKSR1) translocates from the cytoplasm to the plasma membrane in the p resence of activated Ras. At the membrane, mKSR1 modulates Ras signali ng by enhancing Raf-1 activity in a kinase-independent manner, The act ivation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide, These find ings reveal another point of regulation for Ras-mediated signal transd uction and further define a noncatalytic role for mKSR1 in the multist ep process of Raf-1 activation.