THE protein Raf-1, a key mediator of mitogenesis and differentia-tion, associates with p21ras (refs 1-3). However, the regulation of the serine/threonine kinase activity of Raf-1 is still not understood4 13. Using the yeast two-hybrid system8'14-16, we identi-fied two structurally related proteins that interact with the amino-terminal region of Raf-1. These proteins, 14-3-3 £ (PLA2) and 14-3-3 p (HS1), are members of the 14-3-3 family of proteins17'23. Expression of 14-3-3 proteins in Xenopm oocytes enhanced Raf-1 activity and promoted Raf-1-dependent oocyte maturation. A dominant negative mutant of Raf-1 blocked the effects of 14-3-3 protein.