Oncogenic Ras in the phosphorylation of ribosomal protein S6

Oncogenic Ras, one of the most common oncogenic proteins, is related to about 30% of all human cancers. Oncogenic Ras exerts versatile effects in cells such as proliferation, transformation, and cell cycle arrest. One of the mechanisms by which oncogenic Ras exerts its effects is via regulation of protein synthesis. In the cell, all proteins are synthesized in ribosomes. How oncogenic Ras regulates protein synthesis remains to be elucidated. Our laboratory previously showed that oncogenic Ras induces cell cycle arrest in activated Xenopus egg extracts (cycling extract) and that the induced cell cycle arrest correlates with phosphorylation of a 32 kDa protein. By using a series of different types of gel electrophoresis, protein electro-elution and partial tryptic peptide sequence analysis, the 32 kDa protein has now been identified as S6, a 40S subunit ribosomal protein. It has been shown by others that conditional deletion of a gene encoding S6 in the mammalian cells prevents proliferation, demonstrating the importance of S6 in cell proliferation. Phosphorylation of S6 has been implicated in the regulation of protein synthesis. Thus, our results are consistent with the concept that oncogenic Ras induces S6 phosphorylation to influence protein synthesis, thereby contributing to the cell-cycle arrest.;S6 can be phosphorylated by p90rsk or by p70s6k (S6K) in cells. S6K-dependent S6 phosphorylation has been suggested to enhance the assembly of polysomes synthesizing a specific group of proteins. Whether p90rsk-dependent S6 phosphorylation plays a role in protein synthesis remains unknown. It is important to determine whether the oncogenic Ras-induced phosphorylation of S6 of the 40S subunit of ribosomes in activated egg extracts is dependent on p90rsk or S6K. By using different pathway inhibitors and Western immunoblotting, our results showed that the oncogenic Ras-induced phosphorylation of S6 of the 40S subunit of ribosomes is dependent on p90rsk, but not S6K.;Recent results of nutritional studies have shown that leucine, higher amout found in red meat, can regulate protein synthesis by induction of S6 phosphorylation. As consequence, that leucine may share the similar mechanisms in regulation of protein synthesis, thereby influencing synthesis of proteins that important to cancer development.