Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene expression.
Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene expression.
复制标题
Rac 和 Cdc42 在溶血磷脂酸介导的环加氧酶 2 基因表达中的作用。
DOI：
10.1042/bj3620033
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
M. Goppelt‐Struebe
中科院分区：
文献类型：
--
作者：
A. Hahn;H. Barth;M. Kress;P. Mertens;M. Goppelt‐Struebe
研究Rho蛋白在溶血磷脂酸(LPA)介导的肾小球系膜细胞环氧合酶-2(COX-2)诱导中的作用。以前的研究表明，毒素B是Rho、Rac和Cdc42的抑制剂，可以抑制COX-2的诱导。RhoA在百日咳毒素敏感的LPA信号转导中的作用被来自Clostridium limosum的C3转移酶排除在外，C3转移酶被用作融合毒素C2IN-C3(其中C2IN是肉毒杆菌C2I毒素的一部分)。用C2IN-C3孵育细胞可破坏胞浆肌动蛋白应激纤维，但对COX-2的诱导无影响。同样，COX-2诱导的上游步骤p42/44丝裂原活化蛋白激酶(MAP)的激活被毒素B抑制，但不受C2IN-C3的影响。经B毒素处理后，粘着斑激酶和帕西林在酪氨酸残基上被去磷酸化，肌动蛋白细胞骨架被完全破坏。然而，正如肌动蛋白解聚剂细胞松弛素D所表明的那样，p42/44 MAP-KK激活或COX-2诱导不需要完整的细胞骨架。毒素B不影响LPA受体的功能，因为G(I)介导的细胞内钙释放保持不变。在1h内，毒素B失活并将RhoA和Cdc42转移到细胞膜上。在相同的时间范围内，单糖基化的rac1被降解。细胞毒性坏死性因子1(CNF1)直接刺激Rho蛋白可诱导COX-2的表达，这种表达对PD98059抑制MAP-K通路敏感，但对RhoA激酶的抑制剂不敏感。排除RhoA和非特异性细胞骨架的影响，本研究结果表明Rac和/或CDc42在百日咳毒素敏感的LPA介导的COX-2诱导中起重要作用。
The role of Rho proteins in lysophosphatidic acid (LPA)-mediated induction of cyclo-oxygenase-2 (Cox-2) was investigated in renal mesangial cells. Previous studies had shown that toxin B, an inhibitor of Rho, Rac and Cdc42, suppressed Cox-2 induction. A role for RhoA in pertussis toxin-sensitive LPA signalling was excluded with C3 transferase from Clostridium limosum, used as the fusion toxin C2IN-C3 (where C2IN is part of the C2I toxin of C. botulinum). Incubation of the cells with C2IN-C3 disrupted cytosolic actin stress fibres, but had no effect on Cox-2 induction. Similarly, activation of p42/44 mitogen-activated protein kinase (MAP kinase), an upstream step in Cox-2 induction, was inhibited by toxin B, but not affected by C2IN-C3. Upon treatment with toxin B, focal adhesion kinase and paxillin were dephosphorylated at tyrosine residues and the actin cytoskeleton was completely destroyed. An intact cytoskeleton, however, was not required for p42/44 MAP-kinase activation or Cox-2 induction, as shown by the actin-depolymerizing agent cytochalasin D. Toxin B did not influence functionality of LPA receptors, because G(i)-mediated Ca(2+) release from intracellular stores remained unchanged. Within 1 h, toxin B inactivated and translocated RhoA and Cdc42 to the cellular membranes. Within the same time frame, monoglucosylated Rac1 was degraded. Direct stimulation of Rho proteins by cytotoxic necrotizing factor type 1 (CNF1) induced Cox-2 expression, which was sensitive to inhibition of the MAP-kinase pathway by PD98059, but not to an inhibitor of RhoA kinase. By exclusion of RhoA and non-specific cytoskeletal effects, the results in the present study indicate an important role for Rac and/or Cdc42 in pertussis toxin-sensitive LPA-mediated Cox-2 induction.
登录
查看更多内容
G α 13 的激活突变体可诱导 NIH 3T3 细胞中的 Egr-1、c-fos 和转化。
影响因子：
8
作者：
VaraPrasad,MV;Shore,SK;Dhanasekaran,N
通讯作者：
Dhanasekaran,N
DOI：
10.1172/jci7545
发表时间：
2000-04
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
M. Warny;A. C. Keates;S. Keates;I. Castagliuolo;Jeff Zacks;Samer Aboudola;A. Qamar;C. Pothoulakis;J. Lamont;C. Kelly
通讯作者：
M. Warny;A. C. Keates;S. Keates;I. Castagliuolo;Jeff Zacks;Samer Aboudola;A. Qamar;C. Pothoulakis;J. Lamont;C. Kelly
GTPases 的 Ras 和 Rho 家族对 COX-2 转录的差异调节。
DOI：
10.1006/bbrc.2000.3487
发表时间：
2000
期刊：
Biochemical and biophysical research communications.
影响因子：
--
作者：
Slice,LW;Bui,L;Mak,C;Walsh,JH
通讯作者：
Walsh,JH
粘着斑激酶抑制 Rho 活性以促进粘着斑周转。
影响因子：
4
作者：
Ren,XD;Kiosses,WB;Sieg,DJ;Otey,CA;Schlaepfer,DD;Schwartz,MA
通讯作者：
Schwartz,MA