Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the guanine-nucleotide exchange protein, SOS, identified from molecular dynamics calculations, selective inhibition of oncogenic ras-p21

In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras- p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631-641, 676-691, 718-729, and 994- 1004, which differ in structure between the two complexes. We have now micr oinjected synthetic peptides corresponding to each of these domains into Xe nopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oo cytes subsequently incubated with insulin. We find that the first three pep tides inhibit both oncogenic and wild-type p21-induced oocyte maturation, w hile the last peptide much more strongly inhibits oncogenic p21 protein-ind uced oocyte maturation. These results suggest that each identified SOS regi on is involved in ras-stimulated signal transduction and that the 994-1004 domain is involved uniquely with oncogenic ras-p21 signaling.