Regulation of cell-cell interactions by phosphatidic acid phosphatase 2b/VCIP
Regulation of cell-cell interactions by phosphatidic acid phosphatase 2b/VCIP
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DOI：
10.1093/emboj/cdg165
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发表时间：
2003-04-01
期刊：
影响因子：
11.4
通讯作者：
Wary, KK
中科院分区：
文献类型：
--
作者：
Humtsoe, JO;Feng, S;Wary, KK
我们确定了血管内皮生长因子和I型胶原诱导蛋白（VCIP），也被称为磷脂酸磷酸酶2b（PAP 2b），在血管生成的功能测定。VCIP/PAP 2b显示Arg-Gly-Asp（RGD）细胞粘附序列。免疫沉淀和荧光激活细胞分选分析表明，VCIP-RGD暴露于细胞表面的外部。VCIP的逆转录病毒转导诱导细胞聚集/细胞-细胞相互作用，适度增加p120连环蛋白表达并促进Fak、Akt和GSK 3 β蛋白激酶的活化。此外，重组VCIP的表达促进内皮细胞的粘附、铺展和Fak、Shc、Cas和桩蛋白的酪氨酸磷酸化。GST-VCIP-RGD，而不是GST-VCIP-RGE，特异性地与整联蛋白亚组相互作用，并且这些相互作用被抗α（v）β（3）和抗α（5）β（1）整联蛋白抗体以及PAP 2b/VCIP衍生肽有效地阻断。有趣的是，PAP 2b/VCIP在肿瘤血管中与血管内皮生长因子、血管性血友病因子和α（v）β（3）整联蛋白非常接近地表达。这些发现证明了PAP 2b/VCIP的意想不到的功能，并且代表了理解PAP 2b/VCIP诱导的细胞-细胞相互作用调节特定细胞内信号传导途径的分子机制的重要一步。
We identified vascular endothelial growth factor and type I collagen inducible protein (VCIP), also known as phosphatidic acid phosphatase 2b (PAP2b), in a functional assay of angiogenesis. VCIP/PAP2b exhibits an Arg-Gly-Asp (RGD) cell adhesion sequence. Immunoprecipitation and fluorescence-activated cell sorting analyses demonstrated that VCIP-RGD is exposed to the outside of the cell surface. Retroviral transduction of VCIP induced cell aggregation/cell-cell interactions, modestly increased p120 catenin expression and promoted activation of the Fak, Akt and GSK3beta protein kinases. Furthermore, expression of recombinant VCIP promoted adhesion, spreading and tyrosine phosphorylation of Fak, Shc, Cas and paxillin in endothelial cells. GST-VCIP-RGD, but not GST-VCIP-RGE, specifically interacted with a subset of integrins, and these interactions were effectively blocked by anti-alpha(v)beta(3) and anti-alpha(5)beta(1) integrin antibodies, and by PAP2b/VCIP-derived peptides. Interestingly, PAP2b/VCIP is expressed in close proximity to vascular endothelial growth factor, von Willebrand factor and alpha(v)beta(3) integrin in tumor vasculatures. These findings demonstrate an unexpected function of PAP2b/VCIP, and represent an important step towards understanding the molecular mechanisms by which PAP2b/VCIP-induced cell-cell interactions regulate specific intracellular signaling pathways.