NORMAL AND ONCOGENIC P21(RAS) PROTEINS BIND TO THE AMINO-TERMINAL REGULATORY DOMAIN OF C-RAF-1

In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce g rowth and differentiation signals initiated by tyrosine kinases. The R as polypeptide and the amino-terminal regulatory domain of Raf-1(resid ues 1-257) are shown to interact, directly in vitro and in a yeast exp ression system. Raf-1(1-257) binds GTP-Ras in preference to GDP-Ras, a nd inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1(1-257) and Ras transforming activi ty in parallel.