CHARACTERIZATION OF FULL-LENGTH NEUROFIBROMIN - TUBULIN INHIBITS RAS GAP ACTIVITY
CHARACTERIZATION OF FULL-LENGTH NEUROFIBROMIN - TUBULIN INHIBITS RAS GAP ACTIVITY
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DOI：
10.1002/j.1460-2075.1993.tb05841.x
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发表时间：
1993-05-01
期刊：
影响因子：
11.4
通讯作者：
CLARK, R
中科院分区：
文献类型：
--
作者：
BOLLAG, G;MCCORMICK, F;CLARK, R
全长神经纤维蛋白是Ras原癌基因产物的GTPase激活蛋白（GAP）。因此，调节神经纤维蛋白活性对细胞生长具有重要意义。神经纤维蛋白在昆虫细胞中表达时与微管蛋白共纯化。神经纤维蛋白与微管蛋白的相互作用对微管解聚剂秋水仙碱敏感。即使在低浓度的微管蛋白下，神经纤维蛋白GAP活性也受到抑制。然而，对GAP活性的最大抑制仅约为70%，这表明神经纤维蛋白-微管蛋白复合物保留了剩余的GAP活性。这种活性降低反映在它对Ras的亲和力降低了4倍。神经纤维蛋白的截断突变体对微管蛋白的敏感性降低，将一些微管蛋白结合决定因子定位在紧邻gap相关结构域的n端80残基段上。由于微管蛋白是真核细胞中丰富的蛋白质，微管蛋白与神经纤维蛋白的相互作用可能调节Ras信号
Full-length neurofibromin is a GTPase activating protein (GAP) for the Ras proto-oncogene product. Regulation of neurofibromin activity therefore has important implications for cell growth. Neurofibromin co-purifies with tubulin when expressed in insect cells. The interaction between neurofibromin and tubulin is sensitive to the microtubule depolymerizing agent colchicine. Neurofibromin GAP activity is inhibited even at low concentrations of tubulin. However, maximal inhibition of GAP activity is only approximately 70%, suggesting that the neurofibromin-tubulin complex retains residual GAP activity. This decreased activity is reflected by a 4-fold decrease in its affinity for Ras. A truncated mutant of neurofibromin with reduced sensitivity to tubulin localizes some tubulin-binding determinants to an 80 residue segment immediately N-terminal to the GAP-related domain. Since tubulin is an abundant protein in eukaryotic cells, the tubulin-neurofibromin interaction may regulate the Ras signalling