Abstract
Ha-ras is a member of a multigene family in man which encode highly related proteins of 189 amino acids (p21)1–6. In vitro, ras proteins bind GTP7–9, and p21 mutants with threonine at position 59 autophosphorylate at that residue10–12. Mutation (at amino acids 12 or 61)6,13–6 and elevated expression17 of ras genes result in cell transformation in culture, and are also observed in many types of human tumours18. Normal and mutant transforming ras proteins show no differences in localization, lipidation or GTP binding9. However, mutations at position 12 in recombinant (Thr59) p21 molecules were observed to affect autophosphorylation12. We have expressed the full-length normal and T24 transforming (Gly → Val at position 12) Ha-ras proteins in Escherichia coli and have purified them to homogeneity (ref. 19 and M.G. et al., in preparation); these proteins bound GTP with approximately molar stoichiometry and with an affinity comparable to partially purified mammalian proteins. Microinjection of the T24 protein into quiescent rodent fibroblasts resulted in a rapid alteration in cell morphology, stimulation of DNA synthesis and cell division19; in contrast, little response was observed with the normal protein. We now report that the normal ras protein has an intrinsic GTPase activity, yielding GDP and Pi. In contrast, the T24 transforming protein is reduced 10-fold in this activity. We suggest that this deficiency in GTPase is the probable cause for the transforming phenotype of the T24 protein.
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Sweet, R., Yokoyama, S., Kamata, T. et al. The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature 311, 273–275 (1984). https://doi.org/10.1038/311273a0
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DOI: https://doi.org/10.1038/311273a0
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