A conserved region of c-Ha-Ras is required for efficient GTPase stimulation by GTPase activating protein but not neurofibromin.
A conserved region of c-Ha-Ras is required for efficient GTPase stimulation by GTPase activating protein but not neurofibromin.
复制标题
GTPase 激活蛋白（而非神经纤维蛋白）有效刺激 GTPase 需要 c-Ha-Ras 的保守区域。
DOI：
10.1074/jbc.270.46.27615
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Stacey,DW
中科院分区：
文献类型：
--
作者：
Yoder-Hill,J;Golubic,M;Stacey,DW
The effector binding domain and the switch II region of c-Ha-Ras are necessary for p120GAP-stimulated GTP hydrolysis. We report a third region of c-Ha-Ras located within the α3 helix (amino acids 101-103) which is also required for efficient p120GAP, but not neurofibromin-mediated hydrolysis. This highly conserved region of the Ras protein was investigated using an insertion-deletion mutant (Ras-100LIR104) originally characterized by Willumsenet al.(Willumsen, B. M., Adari, H., Zhang, K., Papageorge, A. G., Stone, J. C., McCormick, F., and Lowy, D. R(1989) inThe Guanine Nucleotide Binding Proteins; Common Structural and Functional Properties(Bosch, L., Kraal, B., and Parmeggiani, A., eds) pp. 165-178, Plenum Press, New York). The 100LIR104 substitution did not alter the intrinsic hydrolytic rate of the protein. The p120GAP-stimulated hydrolysis of Ras-100LIR104, however, was decreased by 2-3-fold compared to wild type Ras. This decrease in p120GAP-stimulated hydrolysis was not due to its inability to physically associate with Ras-100LIR104•GTP (as determined by competitive binding assays). Surprisingly, neurofibromin-stimulated GTP hydrolysis was unaltered by the mutation. Finally, no differences were observed in the ability of either the p120GAPcatalytic domain or the neurofibromin GRD to accelerate Ras-100LIR104 GTPase activity, indicating that the amino-terminal noncatalytic GAP region is critical for p120GAP-stimulated GTP hydrolysis. This is the first report of a Ras mutation which differentiates between p120GAPand neurofibromin activity.
