Effect of synthetic peptides representing the hypervariable region of p21ras on Xenopus laevis oocyte maturation.

The carboxy-terminal hypervariable regions of p21ras proteins have been highly conserved throughout evolution but no function has been assigned to them yet. This region has been suggested as a possible candidate for receptor recognition. We have tested the possibility of this region being involved in p21ras biological function. Synthetic peptides corresponding to the hypervariable domains of p21N-ras and p21K(B)-ras were microinjected into Xenopus oocytes to assess their effect on oocyte maturation. The K(B)-ras peptide inhibited insulin-dependent but not progesterone-dependent maturation, in contrast with the N-ras peptide which did not inhibit maturation significantly. A control peptide, with the same amino acid composition as the K(B)-ras peptide but with a scrambled sequence, and poly(D,L-lysine) were inactive. Pentalysine had partial activity which may be due to its mimicking the lysine-rich stretch of the K(B)-ras sequence. The data support the hypothesis that the K(B)-ras gene product specifically is involved in transducing the insulin and/or insulin-like growth factor 1 signal.