Arg kinase regulates epithelial cell polarity by targeting β1-integrin and small GTPase pathways.
Arg kinase regulates epithelial cell polarity by targeting β1-integrin and small GTPase pathways.
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DOI：
10.1016/j.cub.2011.08.023
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发表时间：
2011-09-27
期刊：
影响因子：
9.2
通讯作者：
Pendergast, Ann Marie
中科院分区：
文献类型：
--
作者：
Li, Ran;Pendergast, Ann Marie
上皮细胞极性的建立和维持在一定程度上是由黏附受体信号调节的。细胞极性的丧失与多种病理有关，包括各种癌症的发生和发展。β1-整合素黏附受体在细胞极性调节中发挥作用，然而，调控β1-整合素功能并将其连接到极性调节通路中的信号通路的同一性尚不清楚。目前的工作确定了Arg，非受体酪氨酸激酶Abl家族的成员，在调节黏附信号和上皮细胞极性中的作用。在三维(3D)细胞培养模型中，Arg激酶的激活导致顶端-基底端的显著反转。相反，Arg功能的丧失会损害极化上皮囊泡结构的建立。激活的精氨酸激酶破坏β1-整合素信号和定位，并损害Rac1介导层粘连蛋白的组装。活性精氨酸干扰β1-整合素功能，导致部分由RAP1GTP酶信号介导的选择的极性复杂组分的分布改变。虽然极性反转可以被结构性活性的RAP1部分挽救，但依赖于RAP1的层粘连蛋白组装不能，这表明RAP1和RAC1信号在上皮极性中是独立的。这些发现表明，Arg激酶功能的调节可能不仅有助于正常的上皮极性调节，还可能促进与细胞极性丧失相关的病理改变。
Establishment and maintenance of epithelial cell polarity is regulated in part by signaling from adhesion receptors. Loss of cell polarity is associated with multiple pathologies including the initiation and progression of various cancers. The β1-integrin adhesion receptor plays a role in the regulation of cell polarity; however, the identity of the signaling pathways that modulate β1-integrin function and connect it to the regulation of polarity pathways remains largely unknown. The present work identifies a role for Arg, a member of the Abl family non-receptor tyrosine kinases, in the regulation of adhesive signals and epithelial cell polarity. In a three-dimensional (3D) cell culture model, activation of Arg kinase leads to a striking inversion of apical-basal polarity. In contrast, loss of Arg function impairs the establishment of a polarized epithelial cyst structure. Activated Arg kinase disrupts β1-integrin signaling and localization and impairs Rac1-mediated laminin assembly. Disruption of β1-integrin function by active Arg results in altered distribution of selected polarity complex components mediated in part by Rap1 GTPase signaling. Whereas polarity inversion is partially rescued by a constitutively active Rap1, Rac1-dependent laminin assembly is not, indicating Rap1 and Rac1 signal independently during epithelial polarity. These findings suggest that modulation of Arg kinase function may contribute not only to normal epithelial polarity regulation, but also may promote pathologies associated with loss of cell polarity.
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影响因子：
6.6
作者：
Simpson, L;He, X;Bergan, RC
通讯作者：
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DOI：
10.1083/jcb.200301133
发表时间：
2003-04-28
期刊：
The Journal of cell biology
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DOI：
10.1083/jcb.200801121
发表时间：
2008-09-22
期刊：
The Journal of cell biology
影响因子：
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