Integrin beta 1 cytoplasmic domain dominant negative effects revealed by lysophosphatidic acid treatment.
Integrin beta 1 cytoplasmic domain dominant negative effects revealed by lysophosphatidic acid treatment.
复制标题
溶血磷脂酸治疗揭示了整合素β1细胞质结构域显性负面影响。
DOI：
10.1091/mbc.5.11.1215
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发表时间：
1994
影响因子：
3.3
通讯作者：
Marcantonio,EE
中科院分区：
文献类型：
--
作者：
Smilenov,L;Briesewitz,R;Marcantonio,EE
整合素受体定位于局部接触部位，并通过β1胞质结构域与细胞骨架相互作用。为了研究该结构域在黏附中的作用，我们在NIH3T3细胞中表达了一个由白细胞介素2受体α亚单位胞外和跨膜结构域组成的cDNA，该结构域连接到整合素β1细胞质结构域(IL2R-β1)。由于嵌合蛋白的胞外区在黏附中没有作用，该蛋白质可以将黏附从细胞内事件中解脱出来。正如预期的那样，在表达IL2R-β1的细胞系中，该嵌合体被定向到局部接触部位。出乎意料的是，细胞与纤维连接蛋白(FN)的粘附性正常。然而，当溶血磷脂酸(LPA)诱导细胞骨架的快速重组时，IL2R-β1细胞从FN分离，而不是野生型细胞。肌动蛋白聚合的抑制剂细胞松弛素D可阻止LPA引起的细胞脱离。这些结果表明，从黏附中解偶联的β1胞质结构域可以与天然整合素β1的胞质结构域竞争细胞骨架蛋白。因此，IL2R-β1蛋白通过破坏整合素-细胞骨架连接而成为粘连的主要负面效应因子。
Integrin receptors localize to focal contact sites and interact with the cytoskeleton via the beta 1 cytoplasmic domain. To study the role of this domain in adhesion, we have expressed in NIH 3T3 cells a cDNA consisting of the interleukin 2 receptor alpha subunit extracellular and transmembrane domains, connected to the integrin beta 1 cytoplasmic domain (IL2R-beta 1). Since the extracellular domain of the chimeric protein has no role in adhesion, this protein could uncouple adhesion from intracellular events. As expected, in a cell line expressing IL2R-beta 1, this chimera was directed to focal contact sites. Unexpectedly, the cells exhibited normal adhesion to fibronectin (FN). However, when a rapid reorganization of the cytoskeleton was induced using lysophosphatidic acid (LPA), IL2R-beta 1 cells detached from FN in contrast to wild-type cells. The detachment in response to LPA could be prevented with cytochalasin D, an inhibitor of actin polymerization. These results imply that a beta 1 cytoplasmic domain, which is uncoupled from adhesion, can compete with the cytoplasmic domain of native integrin beta 1 for cytoskeletal proteins. As a consequence, the IL2R-beta 1 protein acts as a dominant negative effector of adhesion by disrupting the integrin-cytoskeleton connection.