Identification of a human rasGAP-related protein containing calmodulin-binding motifs.
Identification of a human rasGAP-related protein containing calmodulin-binding motifs.
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发表时间：
1994-08
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通讯作者：
L. Weissbach;J. Settleman;M. Kalady;A. Snijders;A. Murthy;Yu-xin Yan;A. Bernards
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作者：
L. Weissbach;J. Settleman;M. Kalady;A. Snijders;A. Murthy;Yu-xin Yan;A. Bernards
活性GTP结合型Ras向其非活性GDP结合型的转化由GTP酶激活蛋白（GAP）催化。两种哺乳动物Ras特异性GAP，p120 GAP和神经纤维蛋白，NF 1肿瘤抑制基因的产物，以前已经描述过。我们在这里报告的识别一个新的人类cDNA克隆，IQGAP 1，它预测一个1657个氨基酸的蛋白质，显示广泛的序列相似性的催化结构域的所有以前报道的RasGAP。IQGAP 1与粟酒裂殖酵母RasGAP样蛋白Sar 1关系最为密切。与IQGAP 1的序列相似性见于整个Sar 1蛋白。IQGAP 1的N-末端的一半，不与Sar 1重叠，包含六个拷贝的独特氨基酸基序，以及四个所谓的IQ基序。后一种基序存在于几种蛋白质中，包括常规和非常规肌球蛋白，并介导与钙调蛋白和钙调蛋白相关蛋白的相互作用。因此，IQGAP 1似乎代表了一种新的RasGAP样蛋白，可能将Ras信号传导与某些钙调素介导的过程联系起来。
Conversion of active GTP-bound Ras to its inactive GDP-bound form is catalyzed by GTPase-activating proteins (GAPs). Two mammalian Ras-specific GAPs, p120GAP and neurofibromin, the product of the NF1 tumor suppressor gene, have been previously described. We report here the identification of a new human cDNA clone, IQGAP1, which predicts a 1657-amino acid protein that displays extensive sequence similarity to the catalytic domain of all previously reported RasGAPs. IQGAP1 is most closely related to the Schizosaccharomyces pombe RasGAP-like protein, Sar1. Sequence similarity to IQGAP1 is seen throughout the entire Sar1 protein. The N-terminal half of IQGAP1, which does not overlap with Sar1, contains six copies of a unique amino acid motif, as well as four so-called IQ motifs. The latter motifs are found in several proteins, including conventional and unconventional myosins, and mediate the interaction with calmodulin and calmodulin-related proteins. Thus, IQGAP1 appears to represent a novel RasGAP-like protein that may link Ras signaling to some calmodulin-mediated process.