Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors.
Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors.
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DOI：
10.1083/jcb.200404068
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发表时间：
2004-10-11
期刊：
影响因子：
--
通讯作者：
Cooper JA
中科院分区：
文献类型：
--
作者：
Arthur WT;Quilliam LA;Cooper JA
ras相关的GTPase Rap1在各种哺乳动物细胞类型中刺激整合素介导的粘附和扩散。在这里，我们证明Rap1通过定位鸟嘌呤核苷酸交换因子（gef）来调节细胞扩散，该因子通过Rho家族GTPase Rac1起作用。Rap1a激活Rac1，需要Rac1来促进扩散，而Rac1独立于Rap1诱导扩散。活性Rap1a结合Rac gef的一个子集，包括VAV2和Tiam1，但不结合其他如SWAP-70或COOL-1。过表达的VAV2和Tiam1特异性地需要Rap1来促进传播，尽管Rac1是独立于Rap1激活的。Rap1是VAV2在细胞周围膜突起中积累所必需的。此外，如果将VAV2人工定位到Rap1a亚细胞靶向结构域的细胞边缘，它会独立于Rap1增加细胞扩散。这些结果使我们提出Rap1通过将Rac gef的一个子集定位到活跃板足延伸的位置来促进细胞扩散。
The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell spreading by localizing guanine nucleotide exchange factors (GEFs) that act via the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery. In addition, if VAV2 is artificially localized to the cell edge with the subcellular targeting domain of Rap1a, it increases cell spreading independently of Rap1. These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension.
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影响因子：
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