Ernkvist Mira, Aase Karin, Ukomadu Chinwe, Wohlschlegel James, Blackman Ryan, Veitonmäki Niina, Bratt Anders, Dutta Anindya, Holmgren Lars
Department of Oncology-Pathology, Cancer Centre Karolinska Institute, Stockholm, Sweden.
FEBS J. 2006 May;273(9):2000-11. doi: 10.1111/j.1742-4658.2006.05216.x.
Angiomotin, an 80 kDa protein expressed in endothelial cells, promotes cell migration and invasion, and stabilizes tube formation in vitro. Angiomotin belongs to a new protein family with two additional members, Amotl-1 and Amotl-2, which are characterized by conserved coiled-coil domains and C-terminal PDZ binding motifs. Here, we report the identification of a 130 kDa splice isoform of angiomotin that is expressed in different cell types including vascular endothelial cells, as well as cytotrophoblasts of the placenta. p130-Angiomotin consists of a cytoplasmic N-terminal extension that mediates its association with F-actin. Transfection of p130-angiomotin into endothelial cells induces actin fiber formation and changes cell shape. The p130-angiomotin protein remained associated with actin after destabilization of actin fibers with cytochalasin B. In contrast to p80-angiomotin, p130-angiomotin does not promote cell migration and did not respond to angiostatin. We propose that p80- and p130-angiomotin play coordinating roles in tube formation by affecting cell migration and cell shape, respectively.
血管动蛋白是一种在内皮细胞中表达的80 kDa蛋白质，可促进细胞迁移和侵袭，并在体外稳定管腔形成。血管动蛋白属于一个新的蛋白质家族，还有另外两个成员，即Amotl-1和Amotl-2，其特征是具有保守的卷曲螺旋结构域和C末端PDZ结合基序。在此，我们报告了一种130 kDa血管动蛋白剪接异构体的鉴定，该异构体在包括血管内皮细胞以及胎盘的细胞滋养层细胞在内的不同细胞类型中表达。p130-血管动蛋白由一个细胞质N末端延伸组成，该延伸介导其与F-肌动蛋白的结合。将p130-血管动蛋白转染到内皮细胞中可诱导肌动蛋白纤维形成并改变细胞形状。在用细胞松弛素B使肌动蛋白纤维不稳定后，p130-血管动蛋白仍与肌动蛋白结合。与p80-血管动蛋白不同，p130-血管动蛋白不促进细胞迁移，也不响应血管抑素。我们认为，p80-和p130-血管动蛋白分别通过影响细胞迁移和细胞形状在管腔形成中发挥协同作用。
