The Ras-related protein Rad associates with the cytoskeleton in a non-lipid-dependent manner

被引:28
作者
Bilan, PJ
Moyers, JS
Kahn, CR
机构
[1] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA
关键词
D O I
10.1006/excr.1998.4092
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Rad is the prototypic member of a new family of Ras-related proteins (Rad, Gem, and Kir) which lack typical C-terminal amino acid motifs for isoprenylation, In mouse C2C12 muscle cell Lines about 50% of Rad protein resides in the cytosol and behaves as a hydrophilic protein partitioning away from TX-114. The remainder of Rad is associated with plasma and internal membranes. The association of Rad with the membrane does not occur through the lipid bilayer, but instead depends on the interaction of Rad with the cytoskeleton or membrane skeleton. In contrast to Ras, biosynthetic labeling of cellular proteins in C2C12 cells with [H-3]palmitic acid demonstrates that Rad is not modified with this fatty acid, and inhibition of isoprenylation with lovastatin treatment has no effect on Rad subcellular distribution. Furthermore, removal of the C-terminal 11 amino acids that are precisely conserved in all three Rad family members has no effect on Rad subcellular distribution. Addition of the 9 amino acids from the C-terminus of H-Ras to the truncated Rad protein results in a redistribution of Rad from the cytosol to the membrane skeleton without the presence of any detectable lipid modification of the chimeric protein. These data suggest that Rad possesses unique cellular localization signals which, in contrast to other Ras-related family members, do not depend on the lipid modification of the C-terminus. (C) 1998 Academic Press.
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收藏
页码:391 / 400
页数:10
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