检索结果-内蒙古大学图书馆

Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第1期268卷 141-147页

作者： Kato, J Kaziro, Y Satoh, T Tokyo Inst Technol Fac Biosci & Biotechnol Tokyohama 2268501 Japan

Signals triggered by diverse receptors modulate the activity of Rho family proteins, although the regulatory mechanism remains largely unknown. On the basis of their biochemical activity as guanine nucleotide exchange factors (GEFs), Dbl family proteins are believed to be implicated in the regulation of Rho family GTP-binding proteins in response to a variety of extracellular stimuli. Here we show that GEF activity of full-length proto-Dbl is enhanced upon tyrosine phosphorylation. When transiently coexpressed with the activated form of the non-receptor tyrosine kinase ACK1, a downstream target of Cdc42, Dbl became tyrosine-phosphorylated. In vitro GEF activity of Dbl toward Rho and Cdc42 was augmented following tyrosine phosphorylation. Moreover, accumulation of the GTP-bound form of Rho and Rac within the cell paralleled ACK-1-dependent tyrosine phosphorylation of Dbl. Consistently, activation of c-Jun N-terminal kinase downstream of Rho family GTP-binding proteins was also enhanced when Dbl was tyrosine-phosphorylated. Collectively, these findings suggest that the tyrosine kinase ACK1 may act as a regulator of Dbl, which in turn activates Rho family proteins. (C) 2000 Academic Press.

关键词： COS细胞细胞系酶激活鸟嘌呤核苷酸交换因子类/化学鸟嘌呤核苷酸交换因子类/遗传学鸟嘌呤核苷酸交换因子类/代谢磷酰化蛋白酪氨酸激酶类/遗传学蛋白酪氨酸激酶类/代谢原癌基因蛋白质类/化学原癌基因蛋白质类/遗传学原癌基因蛋白质类/代谢重组蛋白质类/化学重组蛋白质类/遗传学重组蛋白质类/代谢信号传导转染酪氨酸/代谢 cdc42GTP结合蛋白质/遗传学 cdc42GTP结合蛋白质/代谢 ρagtp结合蛋白质/遗传学 ρagtp结合蛋白质/代谢动物人类

来源：评论

学校读者我要写书评

暂无评论

Functional analysis of ARHGAP6, a novel GTPase-activating protein for RhoA

引用

HUMAN MOLECULAR GENETICS 2000年第4期9卷 477-488页

作者： Prakash, SK Paylor, R Jenna, S Lamarche-Vane, N Armstrong, DL Xu, BS Mancini, MA Zoghbi, HY Baylor Coll Med Dept Mol & Human Genet Houston TX 77030 USA Baylor Coll Med Dept Cell Biol Houston TX 77030 USA Baylor Coll Med Dept Pathol Houston TX 77030 USA Baylor Coll Med Howard Hughes Med Inst Houston TX 77030 USA McGill Univ Dept Anat & Cell Biol Montreal PQ Canada

Microphthalmia with linear skin defects (MLS) is an X-linked dominant, male-lethal syndrome characterized by microphthalmia, aplastic skin and agenesis of the corpus callosum, and is caused by the deletion of a 500 kb critical region in Xp22.3. Our laboratory isolated a novel rho GTPase-activating protein (rhoGAP) gene named ARHGAP6 from the MLS region. ARHGAP6 contains 14 exons encoding a 974 amino acid protein with three putative SH3-binding domains. Because exons 2-14 are deleted in all MLS patients, we hypothesized that ARHGAP6 may be responsible for some of the phenotypic features of MLS. We pursued two approaches to study the function of ARHGAP6 and its role in the pathogenesis of MLS: gene targeting of the rhoGAP domain in mouse embryonic stem cells and in vitro expression studies, Surprisingly, loss of the rhoGAP function of Arhgap6 does not cause any detectable phenotypic or behavioral abnormalities in the mutant mice, Transfected mammalian cells expressing ARHGAP6 lose their actin stress fibers, retract from the growth surface and extend thin, branching processes resembling filopodia, The ARHGAP6 protein co-localizes with actin filaments through an N-terminal domain and recruits F-actin into the growing processes, Mutation of a conserved arginine residue in the rhoGAP domain prevents the loss of stress fibers but has little effect on process outgrowth. These results suggest that ARHGAP6 has two independent functions: one as a GAP with specificity for RhoA and the other as a cytoskeletal protein that promotes actin remodeling.

关键词：内含子小鼠近交C57BL 小鼠基因敲除小眼/遗传学小眼/病理学小眼/病理生理学分子序列数据肌骨骼/畸形肌骨骼/病理学肽碎片/生理学 cdc42GTP结合蛋白质/生理学 rac1GTP结合蛋白质/生理学 ρagtp结合蛋白质/缺乏 ρagtp结合蛋白质/遗传学人类男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo

引用

NATURE NEUROSCIENCE 2000年第3期3卷 217-225页

作者： Li, Z Van Aelst, L Cline, HT Cold Spring Harbor Lab Cold Spring Harbor NY 11724 USA SUNY Stony Brook Dept Neurobiol & Behav Stony Brook NY 11794 USA

The development and structural plasticity of dendritic arbors are governed by several factors, including synaptic activity, neurotrophins and other growth-regulating molecules. The signal transduction pathways leading to dendritic structural changes are unknown, but likely include cytoskeleton regulatory components. To test whether GTPases regulate dendritic arbor development, we collected time-lapse images of single optic tectal neurons in albino Xenopus tadpoles expressing dominant negative or constitutively active forms of Rac, Cdc42 or RhoA. Analysis of images collected at two-hour intervals over eight hours indicated that enhanced Rac activity selectively increased branch additions and retractions, as did Cdc42 to a lesser extent. Activation of endogenous RhoA decreased branch extension without affecting branch additions and retractions, whereas dominant-negative RhoA increased branch extension. Finally, we provide data suggesting that RhoA mediates the promotion of normal dendritic arbor development by NMDA receptor activation.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学肌动蛋白类/代谢细胞大小/药物作用细胞骨架/药物作用细胞骨架/代谢树突/药物作用树突/酶学树突/生理学树突/超微结构酶激活/遗传学基因显性/遗传学幼虫/细胞学幼虫/药物作用突变/遗传学神经元可塑性/药物作用受体 N-甲基-D-天冬氨酸/拮抗剂和抑制剂受体 N-甲基-D-天冬氨酸/生理学重组融合蛋白质类/遗传学重组融合蛋白质类/代谢信号传导/药物作用痘苗病毒/遗传学爪蟾光滑 cdc42GTP结合蛋白质/遗传学 cdc42GTP结合蛋白质/代谢 racGTP结合蛋白质类/遗传学 racGTP结合蛋白质类/代谢 ρGTP结合蛋白质类/遗传学 ρGTP结合蛋白质类/代谢 ρagtp结合蛋白质/遗传学 ρagtp结合蛋白质/代谢动物人类

来源：评论

学校读者我要写书评

暂无评论

Genetic analysis demonstrates a direct link between Rho signaling and nonmuscle myosin function during Drosophila morphogenesis

引用

GENETICS 2000年第3期155卷 1253-1265页

作者： Halsell, SR Chu, BI Kiehart, DP Duke Univ Med Ctr Dept Cell Biol Durham NC 27710 USA

A dynamic actomyosin cytoskeleton drives many morphogenetic events. Conventional nonmuscle myosin-II (myosin) is a key chemomechanical motor that drives contraction of the actin cytoskeleton. We have explored the regulation of myosin activity by performing genetic screens to identify gene products that collaborate with myosin during Drosophila morphogenesis. Specifically, we screened for second-site noncomplementors of a mutation in the zipper gene that encodes the nonmuscle myosin-II heavy chain. We determined. that a single missense mutation in the zipper(Ebr) allele gives rise to its sensitivity to second-site noncomplementation. Mie then identify the Rho signal transduction path way as necessary for proper myosin function. First we show that a lethal P-element insertion interacts genetically with zipper. Subsequently we show that this second-site noncomplementing mutation disrupts the RhoGEF2 locus. Next, we show that two EMS-induced mutations, previously shown to interact genetically with zipper(Ebr) disrupt the RhoA locus. Further, we have identified their molecular lesions and determined that disruption of the carboxyl-terminal CaaX box gives rise to their mutant phenotype. Finally, we show that RhoA mutations themselves can be utilized in genetic screens. Biochemical and cell analyses suggest that Rho signal transduction regulated the activity of myosin. Our studies provide direct genetic proof of the biological relevance of regulation of myosin by Rho signal transduction in an intact metazoan.

关键词：等位基因染色体/遗传学果蝇蛋白质类黑腹果蝇/胚胎学黑腹果蝇/遗传学黑腹果蝇/代谢遗传互补测验鸟嘌呤核苷酸交换因子类/遗传学鸟嘌呤核苷酸交换因子类/代谢免疫印迹法膜蛋白质类/遗传学形态发生/遗传学突变误义肌球蛋白重链/遗传学肌球蛋白类/代谢物理染色体图蛋白质结构三级/遗传学信号传导/遗传学 ρagtp结合蛋白质/遗传学动物

来源：评论

学校读者我要写书评

暂无评论

Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia

引用

BLOOD 2000年第9期95卷 2947-2953页

作者： Kasper, B Tidow, N Grothues, D Welte, K Hannover Med Sch Dept Pediat Hematol Oncol D-3000 Hannover Germany

Severe congenital neutropenia (SCN) or Kostmann syndrome is a disorder of myelopoiesis characterized by a maturation arrest at the stage of promyelocytes or myelocytes in bone marrow and absolute neutrophil counts less than 200/mu L in peripheral blood. Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients. To date, little is known regarding the underlying pathomechanism of SCN, G-CSF-induced neutrophils of patients with SCN are functionally defective (eg, chemotaxis, superoxide anion generation, Ca++ mobilization), Two guanosine triphosphatases (GTPases), Rac2 and RhoA, were described to be involved in many neutrophil functions. The expression of these GTPases and their regulation in patients' neutrophils were of interest. This study determined that the guanosine diphosphate (GDP)-dissociation inhibitor RhoGDI is overexpressed at the protein level in patients' neutrophils and that overexpression is a result of G-CSF treatment. RhoA and LyGDI are expressed at similar levels, whereas Rac2 shows a decreased expression. In addition, association of Rac2 and RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression in patients' neutrophils, (Blood, 2000;95: 2947-2953) (C) 2000 by The American Society of Hematology.

关键词：鸟嘌呤核苷酸游离阻滞剂/血液鸟嘌呤核苷酸游离阻滞剂/遗传学中性粒细胞减少/血液中性粒细胞减少/先天性中性粒细胞减少/遗传学中性白细胞/代谢磷酸酪氨酸/血液蛋白质类/遗传学蛋白质类/代谢参考值逆转录聚合酶链反应肿瘤抑制蛋白质类 racGTP结合蛋白质类/血液 racGTP结合蛋白质类/遗传学 ρGTP结合蛋白质类/血液 ρGTP结合蛋白质类/遗传学 ρagtp结合蛋白质/血液 ρagtp结合蛋白质/遗传学人类

来源：评论

学校读者我要写书评

暂无评论

Deamidation of RhoA glutamine 63 by the Escherichia coli CNF1 toxin requires a short sequence of the GTPase switch 2 domain

引用

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第2期267卷 588-592页

作者： Flatau, G Landraud, L Boquet, P Bruzzone, M Munro, P Fac Med INSERM U452 F-06107 Nice 2 France

CNF1, a toxin produced by pathogenic Escherichia coli strains, deamidates the RhoA GTP-binding protein glutamine 63 and impairs RhoGAP-mediated GTP hydrolysis resulting in RhoA permanent activation. Using peptides derived from the RhoA sequence, we found that DTAGQEDYDRL (corresponding to RhoA 59-69 residues) was the minimum RhoA-derived peptide which could be deamidated in vitro by the CNF1 catalytic domain (CNF1-Cter), Site-directed mutagenesis outside the RhoA 59-69 sequence had no influence on glutamine 63 deamidation by CNF1-Cter, RhoA proteins with substitutions L57G, D65G, Y66G, or R70G were not affected in their ability to be deamidated by CNF1-Cter, whereas this was abolished by the R68G substitution, Arginine 68 is part of the DYDRL motif that is strictly conserved in Rho, Rac, and Cdc42 but not in other small GTP-binding proteins consistent with the observation that only Rho, Rac, and Cdc42 can be modified by CNF1. (C) 2000 Academic Press.

关键词：氨基酸序列细菌毒素类/代谢细菌毒素类/毒性细胞毒素类/代谢细胞毒素类/毒性大肠杆菌/代谢大肠杆菌/致病力大肠杆菌蛋白质类谷氨酰胺/化学分子序列数据诱变定点肽碎片/化学肽碎片/遗传学肽碎片/代谢蛋白质结构三级 cdc42GTP结合蛋白质/化学 cdc42GTP结合蛋白质/遗传学 cdc42GTP结合蛋白质/代谢 racGTP结合蛋白质类/化学 racGTP结合蛋白质类/遗传学 racGTP结合蛋白质类/代谢 ρagtp结合蛋白质/化学 ρagtp结合蛋白质/遗传学 ρagtp结合蛋白质/代谢

来源：评论

学校读者我要写书评

暂无评论

Essential roles of Drosophila RhoA in the regulation of neuroblast proliferation and dendritic but not axonal morphogenesis

引用

NEURON 2000年第2期25卷 307-316页

作者： Lee, TM Winter, C Marticke, SS Lee, A Luo, LQ Stanford Univ Dept Biol Sci Stanford CA 94305 USA

The pleiotropic functions of small GTPase Rho present a challenge to its genetic analysis in multicellular organisms. We report here the use of the MARCM (mosaic analysis with a repressible cell marker) system to analyze the function of RhoA in the developing Drosophila brain. Clones of cells homozygous for null RhoA mutations were specifically labeled in the mushroom body (MB) neurons of mosaic brains. We found that RhoA is required for neuroblast (Nb) proliferation but not for neuronal survival. Surprisingly, RhoA is not required for MB neurons to establish normal axon projections. However, neurons lacking RhoA overextend their dendrites, and expression of activated RhoA causes a reduction of dendritic complexity. Thus, RhoA is an important regulator of dendritic morphogenesis, while distinct mechanisms are used for axonal morphogenesis.

关键词：动物结构/细胞学动物结构/生长和发育抗代谢药轴突/代谢溴脱氧尿苷细胞分化/生理学细胞分裂/生理学细胞大小/生理学树突/代谢果蝇属基因表达调控发育期突变/生理学神经元/超微结构表型干细胞/超微结构 ρagtp结合蛋白质/遗传学 ρagtp结合蛋白质/代谢动物

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：