The ras Gene Product

Subcellular fractionation and immunofluorescence of normal cellular and viral ras proteins have indicated that p21 is localized on the inner face of the plasma membrane. Both the normal and the mutant ras proteins bind GTP specifically and strongly, but only the normal protein has GTPase activity. 

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Retroviral-Associated Oncogenes That Are Involved in Growth Regulation The src Gene Product The sis Gene Product The erbB Gene Product The ras Gene Product... 

The ras gene product, p21, which is a membrane-associated protein capable of binding and hydrolysing GTP, may function like the postulated GTP-binding pro-... 

Hoshijima, M., Kiknchi, A., Kawata, M., Ohmori, T., Hashimoto, E., Yamamnra, H., and Takai, Y. (1988). Phosphorylation by cyclic AMP-dependent protein kinase of a hnman platelet Mr 22,000 GTP-binding protein (smg p21) having the same pntative effector domain as the ras gene products. Biochem Biophys Res Commun 157 851-860. 

Ballester, R., Furth, M.E., and Rosen, O.M. (1987). Phorbol ester- and protein kinase C-mediated phosphorylation of the cellular Kirsten ras gene product. J Biol Chem 262 2688-2695. 

The production and constitutive activation of Ras° protein are not sufficient to cause transformation of normal cells In a primary (fresh) culture of human, rat, or mouse fibroblasts. Unlike cells In a primary culture, however, cultured 3T3 cells have undergone a loss-of-functlon mutation in the pi6 gene, which encodes a cyclin-kinase inhibitor that restricts progression through the cell cycle. Such cells can grow for an unlimited time in culture If periodically diluted and supplied with nutrients, which normal cells cannot (see Figure 6-37b). These immortal 3T3 cells are transformed Into full-blown tumor cells only when they produce a constltu-tlvely active Ras protein. For this reason, transfection with the ras gene can transform 3T3 cells, but not normal cultured primary fibroblast cells. Into tumor cells. 

An example of a proto-oncogene is the ras gene. This gene codes for a protein called Ras. Mutation of the ras gene leads to production of abnormal Ras, which activates cell division. Mutations of the ras gene are found in 20-30% of all human cancers. 

Wen ST, van Etten RA (1997) The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. Genes Dev 11 2456-2467... 

Harayama S, M Rekik, M Wubbolts, K Rose, RA Leppik, KN Timmis (1989) Characterization of five genes in the upper-pathway operon of TOE plasmid pPWWO from Pseudomonas putida and identification of the gene products. J Bacterial 171 5048-5055. 

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