Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration.
Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration.
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DOI：
10.1083/jcb.200304031
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发表时间：
2003-08-18
期刊：
影响因子：
--
通讯作者：
Ginsberg MH
中科院分区：
文献类型：
--
作者：
Goldfinger LE;Han J;Kiosses WB;Howe AK;Ginsberg MH
整合素协调细胞极性和定向迁移所必需的空间信号传导事件。来自α4整联蛋白的这些信号调节发育中的细胞迁移和白细胞运输。在这里，我们报告说，有效的α4-介导的迁移需要空间控制α4磷酸化的蛋白激酶A，因此局部抑制信号衔接子，桩蛋白，整合素的结合。在迁移的细胞中，磷酸化的α4沿着前缘沿着积聚。通过诱变或抑制蛋白激酶A阻断α4磷酸化可显著降低α4依赖性迁移和板状脂质体稳定性。在体外，α4磷酸化阻断了桩蛋白的结合;我们现在发现桩蛋白和磷酸化的α4在迁移细胞的前缘成不同的簇，而未磷酸化的α4和桩蛋白沿沿着这些细胞的侧缘共定位。此外，加强桩蛋白与α4的结合抑制了迁移并降低了板状脂质体的稳定性。这些结果表明，地形特异性整合素磷酸化可以控制细胞迁移和极化的衔接蛋白结合的空间分离。
Întegrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from α4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient α4-mediated migration requires spatial control of α4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated α4 accumulated along the leading edge. Blocking α4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced α4-dependent migration and lamellipodial stability. α4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-α4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated α4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with α4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding.
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影响因子：
7.8
作者：
Ramos, JW;DeSimone, DW
通讯作者：
DeSimone, DW
DOI：
10.1152/ajpendo.1999.277.2.e208
发表时间：
1999-08-01
影响因子：
5.1
作者：
Ihlemann, J;Ploug, T;Galbo, H
通讯作者：
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影响因子：
4.8
作者：
Han, JW;Liu, SC;Ginsberg, MH
通讯作者：
Ginsberg, MH
DOI：
10.1073/pnas.91.9.3984
发表时间：
1994-04-26
影响因子：
11.1
作者：
SABE, H;HATA, A;HANAFUSA, H
通讯作者：
HANAFUSA, H
影响因子：
20.3
作者：
Rose, DM;Cardarelli, PM;Ginsberg, MH
通讯作者：
Ginsberg, MH