RaplA and p21ras are small molecular weight GTP-binding proteins involved in the regulation of growth and differentiation. The nucleotide-bound state is regulated by guanine nucleotide exchange factors (GEF) and GTPase activating proteins (GAPs). P21ras mutants which are resistant to GAP and thus constitutively active, are found in 30% of the human tumours. Ras-induced transformaton can be suppressed by raplA, which is 50% homologous to p21ras. The striking observation that raplA and p21ras are identical in the putative effector domain raised the possibility that raplA could share the same effector protein(s) and keep them in a non- productive complex. I would like to use this TMR grant to study the role of raplA-interacting proteins in the function of p21ras. Known raplA-binding proteins (pl20GAP, raf and ralGEF) and newly identified raplA- binding proteins will be characterized.