Chen W, Blanc J, Lim L
Institute of Molecular and Cell Biology, National University of Singapore.
J Biol Chem. 1994 Jan 14;269(2):820-3.
Human breakpoint cluster region (bcr) gene product is a member of a group of GTPase-activating proteins that act exclusively on members of the Ras-related Rho subfamily. A complementary DNA was isolated from Caenorhabditis elegans that encoded a polypeptide of 1438 amino acid residues, CeGAP, which contains a domain with sequence similarity to the COOH-terminal segment (GTPase-activating protein region) of Bcr and other known GTPase-activating proteins of the Rho subfamily. It also contains a "pleckstrin homology" motif, present in many signaling proteins including GTPase-activating proteins and nucleotide exchange factors. The Bcr-like domain of CeGAP exhibited activity not only on members of the C. elegans and human Rho subfamily but surprisingly also on C. elegans Ras protein (let-60), human Ras, and Rab3A. CeGAP is therefore the first GTPase-activating protein acting on Ras-related proteins across different subfamilies. Together with the presence of the pleckstrin homology motif, our finding suggests a central and integrative role for CeGAP in a signaling pathway common to Ras and related proteins.
人类断裂点簇集区（bcr）基因产物是一组GTP酶激活蛋白中的一员，这些蛋白仅作用于Ras相关的Rho亚家族成员。从秀丽隐杆线虫中分离出一个互补DNA，它编码一种含有1438个氨基酸残基的多肽CeGAP，该多肽包含一个与Bcr的COOH末端片段（GTP酶激活蛋白区域）以及Rho亚家族其他已知GTP酶激活蛋白具有序列相似性的结构域。它还包含一个“普列克底物蛋白同源性”基序，存在于许多信号蛋白中，包括GTP酶激活蛋白和核苷酸交换因子。CeGAP的Bcr样结构域不仅对秀丽隐杆线虫和人类Rho亚家族成员具有活性，而且令人惊讶的是，对秀丽隐杆线虫Ras蛋白（let-60）、人类Ras和Rab3A也具有活性。因此，CeGAP是第一个作用于不同亚家族中Ras相关蛋白的GTP酶激活蛋白。连同普列克底物蛋白同源性基序的存在，我们的发现表明CeGAP在Ras及相关蛋白共有的信号通路中起核心和整合作用。
