RhoGDI gamma: A GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas
RhoGDI gamma: A GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas
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DOI：
10.1073/pnas.94.9.4279
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Lim, B
中科院分区：
文献类型：
--
作者：
Adra, CN;Manor, D;Lim, B
GDP解离抑制剂（GDI）在调节GTP酶的激活中起主要作用，并且对于GTP酶的细胞区室化也可能至关重要，RhoGDI和GDI/D4是目前已知的GTP酶Rho亚家族的两种GDI，利用它们的cDNA在低严格性下筛选人脑cDNA文库，我们克隆了优先在脑和胰腺中高水平表达的同源cDNA，预测蛋白质，称为 RhoGDI gamma，与 GDI/D4 和 RhoGDI 大约有 50% 相同，与 RhoGDI 相比，它与 CDC42 和 RhoA 的亲和力较低，并且不与 Rac1、Rac2 或 Ras 结合，RhoGDI gamma 充当 CDC42 的 GDI，但效率比 RhoGDI 低约 20 倍。免疫组织化学研究显示该蛋白质在细胞质中的细胞质囊泡集中在细胞核周围，幼仓鼠肾细胞中蛋白质的过度表达导致细胞因应力纤维的损失而聚集，RhoGDI γ 中独特的疏水性氨基末端（在其他两种 RhoGDI 中未见）可以提供一种将 GDI 定位到特定膜区室的机制，从而确定与 RhoGDI 或 GDI/D4 不同的功能。我们的结果提供了证据，表明存在一个 GDI 家族，用于Rho 相关的 GTPases 以及它们在结合亲和力、靶点特异性和组织表达方面的差异，我们建议将 RhoGDI 更名为 RhoGDI alpha，GDID4 更名为 RhoGDI beta，新的 GDI 应扩大这一类重要调节蛋白的研究范围。
GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activation of GTPases and may also be critical for the cellular compartmentalization of GTPases, RhoGDI and GDI/D4 are two currently known GDIs for the Rho-subfamily of GTPases, Using their cDNAs to screen a human brain cDNA library under low stringency, we have cloned a homologous cDNA preferentially expressed at high levels in brain and pancreas, The predicted protein, named RhoGDI gamma, is approximate to 50% identical to GDI/D4 and RhoGDI, It binds to CDC42 and RhoA with less affinity compared with RhoGDI and does not bind with Rac1, Rac2, or Ras, RhoGDI gamma functions as a GDI for CDC42 but with approximate to 20 times less efficiency than RhoGDI, Immunohistochemical studies showed a diffuse punctate distribution of the protein in the cytoplasm with concentration around the nucleus in cytoplasmic vesicles, Overexpression of the protein in baby hamster kidney cells caused the cells to round up with loss of stress fibers, A distinct hydrophobic amino terminus in RhoGDI gamma, not seen in the other two RhoGDIs, could provide a mechanism for localization of the GDI to specific membranous compartment thus determining function distinct from RhoGDI or GDI/D4, Our results provide evidence that there is a family of GDIs for the Rho-related GTPases and that they differ in binding affinity, target specificity, and tissue expression, We propose that RhoGDI be renamed RhoGDI alpha and GDID4 be renamed RhoGDI beta, The new GDI should widen the scope of investigation of this important class of regulatory protein.