title: Identification of amino acids in p21ras involved in exchange factor interaction.
abstract: Through the genetic analysis of vulva development in C. elegans several different sites of mutation have been identified in the let-60 ras protein which have been postulated to affect the function of normal but not oncogenic p21ras (Beitel, G. J., S. G. Clark, and H. R. Horvitz. 1990. Nature 348: 503-509). We have introduced these mutations into mammalian Ha-ras and determined their effect on the function of cellular ras (c-ras), an oncogenically activated variant D12ras and the dominant negative N17ras. From these studies we conclude that two of the mutations S89-->F89 and delta 103-108 destabilise ras when it is in the GDP-bound form. However mutations at A66 and G75 lead to stable proteins on which a ras exchange factor SCD25 is unable to promote the formation of ras-GTP. The mutations at A66 show for the first time that helix alpha 2 of p21ras is involved in the stimulation of guanine nucleotide exchange by exchange factors.
authors.affiliation: Chester Beatty Laboratories, Institute of Cancer Research, London, England.
authors.forename: L R
authors.initials: LR
authors.lastname: Howe
authors.forename: C J
authors.initials: CJ
authors.lastname: Marshall
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras)